Novel Technologies for Recombinant Protein Overexpression in Escherichia coli
Tobias Cornvik
Department of Biochemistry and Biophysics Stockholm University
2006=
= O açÅíçê~ä=qÜÉëáë=OMMS=
aÉé~êíãÉåí=çÑ=_áçÅÜÉãáëíêó=~åÇ=_áçéÜóëáÅë=
qÜÉ=^êêÜÉåáìë=i~Äçê~íçêáÉë=Ñçê=k~íìê~ä=pÅáÉåÅÉë=
píçÅâÜçäã=råáîÉêëáíó=
pbJNMS=VN=píçÅâÜçäã=
pïÉÇÉå==
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
==
=
=
=
=
=
=
=
=
=
^ää=éêÉîáçìëäó=éìÄäáëÜÉÇ=é~éÉêë=~êÉ=êÉéêáåíÉÇ==
ïáíÜ=éÉêãáëëáçå=Ñêçã=íÜÉ=éìÄäáëÜÉêK=
=
açÅìpóëI=píçÅâÜçäã=
=
«=OMMS=qçÄá~ë=`çêåîáâ=
fp_k=VNJTNRRJONOJuI=éé=NJTS=
= P
Abstract
qÜÉ=ìëÉ=çÑ=êÉÅçãÄáå~åí=éêçíÉáå=áë=~=ÅçêåÉêëíçåÉ=áå=ã~åó=ëíêìÅíìê~ä=
~åÇ= ÑìåÅíáçå~ä= ëíìÇáÉëK= qÜÉ= ÉåíÉêáÅ= Ä~ÅíÉêáìã= bëÅÜÉêáÅÜá~= `çäá= áë= íÜÉ=
ãçëí= Åçããçåäó= ìëÉÇ= çêÖ~åáëã= Ñçê= éêçÇìÅáåÖ= êÉÅçãÄáå~åí= éêçíÉáåëK=
bK= Åçäá= Ü~ë= ëÉîÉê~ä= ~Çî~åí~ÖÉë= çîÉê= çíÜÉê= ÉñéêÉëëáçå= ÜçëíëI= Äìí= ~äëç=
çåÉ=ã~àçê=Çáë~Çî~åí~ÖÉ=J=íÜÉ=éêçíÉáå=çÑ=áåíÉêÉëí=ÇçÉë=åçí=~äï~óë=~Ççéí=
áíë=å~íáîÉ=ÅçåÑçêã~íáçåK=fåëíÉ~Ç=íÜÉ=éêçíÉáå=ãáÖÜí=Ñçêã=ä~êÖÉ=áåëçäìÄäÉ=
~ÖÖêÉÖ~íÉëI= áåÅäìëáçå= ÄçÇáÉëI= ïáíÜáå= íÜÉ= ÅÉääK= få= é~êíáÅìä~êI= íÜÉ=
ÜÉíÉêçäçÖçìë=çîÉêÉñéêÉëëáçå=çÑ=Éìâ~êóçíáÅ=~åÇ=ãÉãÄê~åÉ=éêçíÉáåë=~êÉ=
íêçìÄäÉëçãÉK=
få=íÜáë=íÜÉëáëI=ãÉíÜçÇë=~êÉ=ÇÉëÅêáÄÉÇ=íÜ~í=Å~å=ÄÉ=ìëÉÇ=íç=áåÅêÉ~ëÉ=íÜÉ=
äáâÉäáÜççÇ=çÑ=çîÉêÉñéêÉëëáåÖ=Éìâ~êóçíáÅ=éêçíÉáåë=~ë=ïÉää=~ë=ãÉãÄê~åÉ=
éêçíÉáåëK= få= é~êíáÅìä~êI= ~= åçîÉä= ãÉíÜçÇ= áë= ÇÉëÅêáÄÉÇ= íÜ~í= Å~å=
ÇáëíáåÖìáëÜ= ÄÉíïÉÉå= Ä~ÅíÉêá~ä= ÅçäçåáÉë= ÉñéêÉëëáåÖ= ëçäìÄäÉ= éêçíÉáåë=
Ñêçã= íÜçëÉ= ÉñéêÉëëáåÖ= áåÅäìëáçå= ÄçÇáÉëK= qÜÉ= ãÉíÜçÇ= ìíáäáòÉë= íÜÉ= Ñ~Åí=
íÜ~í=áåÅäìëáçå=ÄçÇáÉë=~êÉ=çÑ=~=ÅçåëáÇÉê~ÄäÉ=ëáòÉ=~åÇ=Å~å=ÄÉ=êÉãçîÉÇ=Äó=
Ñáäíê~íáçåK= rëáåÖ= íÜáë= ëÅêÉÉåáåÖ= ãÉíÜçÇ= áå= ÅçãÄáå~íáçå= ïáíÜ= ãÉíÜçÇë=
íÜ~í=~äíÉê=íÜÉ=éÜóëáÅ~ä=éêçéÉêíáÉë=çÑ=éêçíÉáåëI=ïÉ=Ü~îÉ=ëÜçïå=íÜ~í=íÜÉ=
äáâÉäáÜççÇ=çÑ=çîÉêÉñéêÉëëáçå=áå=bK=Åçäá=Å~å=ÄÉ=Çê~ã~íáÅ~ääó=áåÅêÉ~ëÉÇK===
=
= Q
Table of contents
^_pqo^`q KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK P q^_ib=lc=`lkqbkqp KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK Q ifpq=lc=m^mbop KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK R
^__obsf^qflkp KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK S fkqolar`qflkKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK T
molqbfkp... 8
^=efpqlof`^i=mbopmb`qfsb... 10
pqor`qro^i=dbkljf`p... 15
molqbfk=lsbobumobppflkKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK NS qo^kp`ofmqflk... 16
qo^kpi^qflk... 17
cliafkd... 18
bumobppflk=m^o^jbqbopKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK OS bumobppflk=jbaf^L`riqrob=`lkafqflkp=Em^mbo=fF ... 27
pqo^fkp... 28
crpflk=m^oqkbop... 28
plir_fifqv=p`obbkfkd=jbqelap... 30
fk=sfqol=bslirqflkKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK PO `lilkv=p`obbkfkd=jbqelap KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK PP jbqelap=_^pba=lk=obmloqbo=molqbfkp... 33
mbmqfab=_^pba=obmloqbop... 35
qeb=`lilkv=cfiqo^qflk=_ilq=Em^mbo=ffFKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK PU fk=sfqol=bslirqflk=^ka=qeb=`lcf=_ilq=Em^mbo=fffF KKKKKKKKKKKKKKKKKKKKKKKKK QO lsbomolar`qflk=lc=jbj_o^kb=molqbfkpKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK QU afob`qba=bslirqflk=lk=jbj_o^kb=molqbfkp=Em^mbo=fsF ... 51 crqrob=molpmb`qpKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK RT
^`hkltibadjbkqpKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK RU obcbobk`bpKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK SM
=
= R
List of papers
qÜáë=íÜÉëáë=áë=Ä~ëÉÇ=çå=íÜÉ=ÑçääçïáåÖ=é~éÉêëI=êÉÑÉêêÉÇ=íç=áå=íÜÉ=íÉñí=Äó=
íÜÉáê=oçã~å=åìãÉê~äëK=
=
fK== = i~åÖÉ=`I=`çêåîáâ=qI=aá~òJjçêÉåç=f=~åÇ=rÄÄáåâ=jK=
qÜÉ= íê~åëáÉåí= ÅçãéäÉñ= çÑ= éçéä~ê= éä~ëíçÅó~åáå= ïáíÜ=
ÅóíçÅÜêçãÉ=ÑW=ÉÑÑÉÅíë=çÑ=áçåáÅ=ëíêÉåÖíÜ=~åÇ=éeK=
_áçÅÜáãáÅ~= Éí= _áçéÜóëáÅ~= ^Åí~= E__^F= Ó= _áçÉåÉêÖÉíáÅëK=
OMMR=NTMTEOJPFW=NTVJUU=
=
ffK= `çêåîáâ=qI=a~ÜäêçíÜ=piI=j~ÖåìëÇçííáê=^I=eÉêã~å=jaI=
hå~ìëí=oI=bâÄÉêÖ=j=~åÇ=kçêÇäìåÇ=mK=
`çäçåó= Ñáäíê~íáçå= ÄäçíW= ~= åÉï= ëÅêÉÉåáåÖ= ãÉíÜçÇ= Ñçê=
ëçäìÄäÉ=éêçíÉáå=ÉñéêÉëëáçå=áå=bëÅÜÉêáÅÜá~=ÅçäáK=
k~íìêÉ=jÉíÜçÇëK=OMMR=OETFWRMTJVK=
=
fffK= `çêåîáâ= qI= a~ÜäêçíÜ= piI= j~ÖåìëÇçííáê= ^I= cäçÇáå= pI=
båÖî~ää=_I=iáÉì=sI=bâÄÉêÖ=j=~åÇ=kçêÇäìåÇ=mK=
= ^å= ÉÑÑáÅáÉåí= ~åÇ= ÖÉåÉêáÅ= ëíê~íÉÖó= Ñçê= éêçÇìÅáåÖ= ëçäìÄäÉ=
Üìã~å= éêçíÉáåë= ~åÇ= Ççã~áåë= áå= bK= Åçäá= Äó= ëÅêÉÉåáåÖ=
ÅçåëíêìÅí=äáÄê~êáÉëK=
= = pìÄãáííÉÇ=
=
fsK== j~êíáåÉò= jçäáå~= aI= `çêåîáâ=qI= bëÜ~ÖÜá= pI= e~ÉÖÖëíê∏ã=
gwI=kçêÇäìåÇ=m=~åÇ=fÖå~íìëÜÅÜÉåâç=p~ÄÉí=j=
= ^= ÖÉåÉê~ä= ÉåÖáåÉÉêáåÖ= ~åÇ= ëÅêÉÉåáåÖ= ëíê~íÉÖó= Ñçê=
ãÉãÄê~åÉ=éêçíÉáå=çîÉêÉñéêÉëëáçå=áå=bK=ÅçäáK=
= pìÄãáííÉÇ=
=
= S
Abbreviations
Åak^= = `çãéäÉãÉåí~êó=ak^=
`çcá=Ääçí= = `çäçåó=cáäíê~íáçå=_äçí=
`JíÉêãáåìë= = `~êÄçñóJqÉêãáåìë=
aaj== = åJaçÇÉÅóä=≈JaJã~äíçëáÇÉ=
bj= = = bäÉÅíêçå=jáÅêçëÅçéó=
cáaç= = = cáäíê~íáçå=açí=_äçí=
dcm= = = dêÉÉå=cäìçêÉëÅÉåí=mêçíÉáå=
dpq= = = däìí~íÜáçåÉ=ëJqê~åëÑÉê~ëÉ=
fj^`= = fããçÄáäáòÉÇ=jÉí~ä=^ÑÑáåáíó=`Üêçã~íçÖê~éÜó=
j_m= = = j~äíçëÉ=_áåÇáåÖ=mêçíÉáå=
kJíÉêãáåìë= = ^ãáåçJíÉêãáåìë==
kjo== = kìÅäÉ~ê=j~ÖåÉíáÅ=oÉëçå~åÅÉ==
loc=== = léÉå=oÉ~ÇáåÖ=cê~ãÉ=
m`o= = = mçäóãÉê~ëÉ=`Ü~áå=oÉ~Åíáçå=
pd= = = píêìÅíìê~ä=dÉåçãáÅë=
qou= = = qÜáçêÉÇçñáå=
tq= = = táäÇ=qóéÉ=
= T
Introduction
qÜÉ=Üìã~å=ÄçÇó=Åçåëáëíë=çÑ=~ééêçñáã~íÉäó=NMM=íêáääáçå=ENMNQF=ÅÉääë=~åÇ=
~äëç= Üçëíë= ~åçíÜÉê= èì~Çêáääáçå= ENMNRF= ÅÉääë= áå= íÜÉ= Ñçêã= çÑ= ãáÅêçJ çêÖ~åáëãë= íÜ~í=äáîÉ=áå=çìê=Öìí=xNzK= b~ÅÜ=ÅÉää=áë=ëìêêçìåÇÉÇ=Äó= ~=îÉêó=
íÜáå= Ñáäã= çÑ= äáéáÇë= EÑ~íëF= ëÜáÉäÇáåÖ= íÜÉ= áåíÉêáçê= EÅóíçéä~ëãF= Ñêçã= íÜÉ=
ëìêêçìåÇáåÖ=ãÉÇá~K=fåëáÇÉ=íÜÉ=ÅÉää=~êÉ=~=ãóêá~Ç=çÑ=ÇáÑÑÉêÉåí=ãçäÉÅìäÉëX=
ëìÖ~êëI= äáéáÇëI= åìÅäÉçíáÇÉë= EíÜÉ= ÄìáäÇáåÖ= ÄäçÅâë= çÑ= ak^= ~åÇ= ÉåÉêÖó=
Å~êêáÉêë=áå=íÜÉ=ÅÉääFI=éêçíÉáåëI=ak^=EíÜÉ=ÄäìÉéêáåíF=~åÇ=ok^=EÅçéáÉë=çÑ=
ëéÉÅáÑáÅ=êÉÖáçåë=çÑ=íÜÉ=ak^FK=qÜáë=íÜÉëáë=ïáää=ÑçÅìë=çå=íÜÉ=éêçíÉáåëI=íÜÉ=
Ñ~ëÅáå~íáåÖ=ãçäÉÅìäÉë=íÜ~í=éÉêÑçêã=~=ïáÇÉ=î~êáÉíó=çÑ=ÑìåÅíáçåë=áå=íÜÉ=
ÅÉääK= pçãÉ= éêçíÉáåë= ~Åí= ~ë= íê~Åâë= çå= ïÜáÅÜ= ãçäÉÅìä~ê= ãçíçêë= E~äëç=
éêçíÉáåëF=~êÉ=ÖìáÇÉÇK=líÜÉê=éêçíÉáåë=ÄìáäÇ=ìé=íÜÉ=ëìééçêí=çåíç=ïÜáÅÜ=
íÜÉ= äáéáÇ= Äáä~óÉê= áë= ~åÅÜçêÉÇK= mêçíÉáåë= íÜ~í= êÉëáÇÉ= áå= íÜÉ= äáéáÇ= Äáä~óÉê=
~Åíë=~ë=ãçäÉÅìä~ê=ëÉåëçêë=íÜ~í=Å~å=íê~åëÑÉê=ëáÖå~äë=Ñêçã=íÜÉ=çìíëáÇÉ=çÑ=
íÜÉ=ÅÉää=íç=íÜÉ=áåëáÇÉK=^åçíÜÉê=áãéçêí~åí=ÑìåÅíáçå=çÑ=íÜÉ=éêçíÉáåë=áë=íç=
Å~í~äóòÉ= ÅÜÉãáÅ~ä= êÉ~Åíáçåë= ïáíÜáå= íÜÉ= ÅÉääëX= íÜáë= ëéÉÅá~ä= Åä~ëë= çÑ=
éêçíÉáåë=~êÉ=Å~ääÉÇ=ÉåòóãÉëK===
=
qç= ìåÇÉêëí~åÇ= Üçï= ~å= ÉåòóãÉ= çê= ~= êÉÅÉéíçê= ïçêâë= ~í= íÜÉ= ~íçãáÅ=
äÉîÉäI= áíë= íÜêÉÉ= ÇáãÉåëáçå~ä= ëíêìÅíìêÉ= ~í= ~íçãáÅ= êÉëçäìíáçå= Ü~ë= íç= ÄÉ=
ÇÉíÉêãáåÉÇK= qÜÉêÉ= ~êÉ= íÜêÉÉ= ã~áå= ãÉíÜçÇëI= uJê~ó= Åêóëí~ääçÖê~éÜóI=
kjo=~åÇ=ÉäÉÅíêçå=ãáÅêçëÅçéó=íÜ~í=Å~å=ÄÉ=ìëÉÇ=íç=ÇÉíÉêãáåÉ=éêçíÉáå=
ëíêìÅíìêÉëK=få=íÜáë=íÜÉëáë=f=ïáää=~äãçëí=ÉñÅäìëáîÉäó=ÇáëÅìëë=íÜÉ=ìëÉ=çÑ=uJ ê~ó= Åêóëí~ääçÖê~éÜóI= ïÜáÅÜ= áë= íÜÉ= Ççãáå~íáåÖ= ãÉíÜçÇ= Ñçê= ~Ä= áåáíáç=
ëíêìÅíìêÉ= ÇÉíÉêãáå~íáçåK= rëáåÖ= uJê~ó= Åêóëí~ääçÖê~éÜó= íÜÉ= ~íçãáÅ=
ÇÉí~áäë= çÑ= ãçêÉ= íÜ~å= VIMMM= ìåáèìÉ= éêçíÉáå= ëíêìÅíìêÉë= Ü~îÉ= ÄÉÉå=
ÇÉíÉêãáåÉÇNK= uJê~ó= Åêóëí~ääçÖê~éÜó= áë= ~= îÉêó= éçïÉêÑìä= ãÉíÜçÇ= Äìí= áí=
Ü~ë= ëÉîÉê~ä= êÉèìáêÉãÉåíëK= låÉ= êÉèìáêÉãÉåí= áë= íÜ~í= ä~êÖÉ= ~ãçìåíë= çÑ=
éìêÉ=éêçíÉáå=~êÉ=åÉÉÇÉÇK=få=íÜÉ=É~êäó=Ç~óë=çÑ=uJê~ó=Åêóëí~ääçÖê~éÜó=íÜÉ=
éêçíÉáå=ï~ë=éìêáÑáÉÇ=Ñêçã=íÜÉ=å~íáîÉ=ëçìêÅÉK=eçïÉîÉêI=íÜáë=ëíê~íÉÖó=áë=
åçí=ìëÉÑìä=Ñçê=ãçëí=éêçíÉáåëK=cçê=áåëí~åÅÉ=áÑ=çåÉ=ïçìäÇ=äáâÉ=íç=ëíìÇó=~=
Üìã~å=éêçíÉáå=áí=ïçìäÇ=ÄÉ=îÉêó=ÅçãéäáÅ~íÉÇI=Ñçê=çÄîáçìë=êÉ~ëçåëI=íç=
=========================================
N=ÜííéWLLïïïKéÇÄKçêÖ=
= U
éìêáÑó=áí=Ñêçã=íÜÉ=ëçìêÅÉI=íÜÉ=Üìã~å=ÄçÇóK=`ìäíìêÉÇ=ã~ãã~äá~å=ÅÉääë=
Å~å=ÄÉ=ìëÉÇ=áåëíÉ~Ç=Äìí=íç=~=îÉêó=ÜáÖÜ=ÅçëíK=
qç=çîÉêÅçãÉ=íÜáë=éêçÄäÉãI=ãÉíÜçÇë=Ü~îÉ=ÄÉÉå=ÇÉîÉäçéÉÇ=íÜ~í=ìíáäáòÉ=
íÜÉ=Ñ~Åí=íÜ~í=~=Ä~ÅíÉêáìã=Å~å=ÄÉ=“íêáÅâÉÇÒ=áåíç=éêçÇìÅáåÖ=íÜÉ=éêçíÉáå=
çÑ=áåíÉêÉëíK=qç=“íêáÅâÒ=íÜÉ=Ä~ÅíÉêá~I=íÜÉ=ak^=ÅçÇáåÖ=Ñçê=íÜÉ=éêçíÉáå=áë=
áåëÉêíÉÇ=áåíç=~=éä~ëãáÇ=E~=ÅáêÅìä~ê=ak^=ãçäÉÅìäÉF=~åÇ=íê~åëÑÉêêÉÇ=áåíç=
íÜÉ=Ä~ÅíÉêá~ä=ÅÉääK=få=íÜÉ=éä~ëãáÇ=íÜÉêÉ=~êÉ=ak^=ÉäÉãÉåíë=íÜ~í=ÑçêÅÉ=íÜÉ=
Ä~ÅíÉêá~=íç=éêçÇìÅÉ=îÉêó=ä~êÖÉ=~ãçìåíë=çÑ=íÜÉ=éêçíÉáå=çÑ=áåíÉêÉëíK=páåÅÉ=
íÜÉ=êÉÅçãÄáå~åí=éêçíÉáå=áë=ÑçêÉáÖå=íç=Ä~ÅíÉêá~=áí=áë=èìáíÉ=Åçããçå=íÜ~í=
íÜÉ= éêçíÉáå= ÇçÉë= åçí= ~Ççéí= ~= å~íáîÉ= ÅçåÑçêã~íáçåK= fåëíÉ~Ç= ä~êÖÉ=
áåëçäìÄäÉ= ~ÖÖêÉÖ~íÉëI= âåçïå= ~ë= áåÅäìëáçå= ÄçÇáÉëI= ~êÉ= ÑçêãÉÇK= qÜÉ=
ïçêâ= áå= íÜáë= íÜÉëáë= ÇÉ~äë= ïáíÜ= íÜÉ= éêçÄäÉã= çÑ= íêóáåÖ= íç= çîÉêéêçÇìÅÉ=
éêçíÉáåë=áå=íÜÉ=Ä~ÅíÉêáìã=bëÅÜÉêáÅÜá~=ÅçäáI=ïÜáÅÜ=åçêã~ääó=êÉëáÇÉë=áå=
çìê=ÖìíK=jçêÉ=ëéÉÅáÑáÅ~ääóI=íÜÉ=íÜÉëáë=ÇÉëÅêáÄÉë=ãÉíÜçÇë=íÜ~í=Ü~îÉ=ÄÉÉå=
ÇÉîÉäçéÉÇ= íç= íêó= íç= áåÅêÉ~ëÉ= íÜÉ= éêçÄ~Äáäáíó= çÑ= çÄí~áåáåÖ= ÅçêêÉÅíäó=
ÑçäÇÉÇ= êÉÅçãÄáå~åí=éêçíÉáå= ~åÇ= ãÉíÜçÇë=íÜ~í= ÇÉ~ä= ïáíÜ= íÜÉ= éêçÄäÉã=
çÑ=áÇÉåíáÑóáåÖ=Ä~ÅíÉêá~ä=ÅçäçåáÉë=íÜ~í=éêçÇìÅÉ=ÅçêêÉÅíäó=ÑçäÇÉÇ=éêçíÉáåëK=
=
Proteins
^ë= ãÉåíáçåÉÇ= áå= íÜÉ= áåíêçÇìÅíáçåI= éêçíÉáåëLéçäóéÉéíáÇÉë= Å~å= ëÉêîÉ= ~=
ïáÇÉ= î~êáÉíó= çÑ= ÑìåÅíáçåë= ~åÇ= Ü~îÉ= ~= ëáòÉ= ê~åÖáåÖ= Ñêçã= àìëí= ~= ÑÉï=
~ãáåç= ~ÅáÇë= EÑçê= íÜÉ= ëã~ääÉëí= éÉéíáÇÉ= ÜçêãçåÉëF= íç= íÜÉ= ÖáÖ~åíáÅ= íáíáå=
éêçíÉáå=ïÜáÅÜ=Ü~ë=OSIVOSJ~ãáåç=~ÅáÇë=~åÇ=~=ãçäÉÅìä~ê=ã~ëë=çÑ=OIVVP=
âa~= xOzK= qÜÉ= ÄìáäÇáåÖ= ÄäçÅâë= çÑ= éêçíÉáåë= ~êÉ= íÜÉ= OM= å~íìê~ääó=
çÅÅìêêáåÖ=~ãáåç=~ÅáÇë=ïÜáÅÜ=~êÉ=àçáåÉÇ=íçÖÉíÜÉê=îá~=~=éÉéíáÇÉ=ÄçåÇ=íç=
Ñçêã=íÜÉ=éçäóéÉéíáÇÉ=ÅÜ~áåK=qÜÉ=ÅÉåíê~ä=ÇçÖã~=çÑ=ãçäÉÅìä~ê=ÄáçäçÖó=
ï~ë=ÉåìåÅá~íÉÇ=Äó=cê~åÅáë=`êáÅâ=áå=NVRU=xPzK=qÜÉ=ÇçÖã~=ÇÉëÅêáÄÉë=íÜÉ=
ï~ó= áå= ïÜáÅÜ= áåÑçêã~íáçå= áë= íê~åëÑÉêêÉÇ= Ñêçã= ak^= îá~= ok^= íç= íÜÉ=
ëóåíÜÉëáë= çÑ= éêçíÉáåëK= qÜÉ= ÄìáäÇáåÖ= ÄäçÅâë= çÑ= ak^= ~êÉ= åìÅäÉçíáÇÉë=
ÅçåëáëíáåÖ= çÑ= ~= éÜçëéÜ~íÉI= ~= ÇÉçñóêáÄçëÉ= ëìÖ~ê= ~åÇ= ~= Ä~ëÉI= ~ÇÉåáåÉ=
E^FI=Öì~åáåÉ=EdF=ÅóíçëáåÉ=E`F=çê=íÜóãáåÉ=EqFK=páåÅÉ=íÜÉêÉ=~êÉ=OM=~ãáåç=
~ÅáÇë=íÜÉ=áåÑçêã~íáçå=Ñêçã=~=ëáåÖäÉ=Ä~ëÉ=áë=åçí=ÉåçìÖÜ=íç=ÅçÇÉ=Ñçê=~ää=
OM= ~ãáåç= ~ÅáÇëK= qÜÉêÉÑçêÉ= ëÉîÉê~ä= Ä~ëÉë= Ü~îÉ= íç= ÄÉ= ìëÉÇ= íç=ÅçÇÉ= Ñçê=
çåÉ= ~ãáåç= ~ÅáÇK= ^= íïçJÄ~ëÉ= ÅçãÄáå~íáçå= ÅçìäÇ= éçíÉåíá~ääó= ÅçÇÉ= Ñçê==
= V
QO=Z=NS=ÇáÑÑÉêÉåí=~ãáåç=~ÅáÇë=EïÜáÅÜ=áë=åçí=ÉåçìÖÜFK=få=Ñ~Åí=íÜÉ=Ä~ëÉë=
~êÉ= ÇÉÅçÇÉÇ= áå= Öêçìéë= çÑ= íÜêÉÉ= ~åÇ= áí= áë= íÜáë= êìäÉI= Üçï= íÜÉ= ÖÉåÉíáÅ=
áåÑçêã~íáçå=ÉåÅçÇÉÇ=áå=íÜÉ=ak^=íÜ~í=áë=Å~ääÉÇ=íÜÉ=ÖÉåÉíáÅ=ÅçÇÉ=Eq~ÄäÉ=
NF=
=
qqq=Z=mÜÉåóä~ä~åáåÉ=
qq`=Z=mÜÉåóä~ä~åáåÉ=
qq^=Z=iÉìÅáåÉ=
qqd=Z=iÉìÅáåÉ=
q`q=Z=pÉêáåÉ=
q``=Z=pÉêáåÉ=
q`^=Z=pÉêáåÉ=
q`d=Z=pÉêáåÉ=
q^q=Z=qóêçëáåÉ=
q^`=Z=qóêçëáåÉ=
q^^=Z=píçé=
q^d=Z=píçé=
qdq=Z=`óëíÉáåÉ=
qd`=Z=`óëíÉáåÉ=
qd^=Z=píçé=
qdd=Z=qêóéíçéÜ~å=
`qq=Z=iÉìÅáåÉ=
`q`=Z=iÉìÅáåÉ=
`q^=Z=iÉìÅáåÉ=
`qd=Z=iÉìÅáåÉ=
``q=Z=mêçäáåÉ=
```=Z=mêçäáåÉ=
``^=Z=mêçäáåÉ=
``d=Z=mêçäáåÉ=
`^q=Z=eáëíáÇáåÉ=
`^`=Z=eáëíáÇáåÉ=
`^^=Z=däìí~ãáåÉ=
`^d=Z=däìí~ãáåÉ=
`dq=Z=^êÖáåáåÉ=
`d`=Z=^êÖáåáåÉ=
`d^=Z=^êÖáåáåÉ=
`dd=Z=^êÖáåáåÉ=
^qq=Z=fëçäÉìÅáåÉ=
^q`=Z=fëçäÉìÅáåÉ=
^q^=Z=fëçäÉìÅáåÉ=
^qd=Z=jÉíÜáçåáåÉLpí~êí=
^`q=Z=qÜêÉçåáåÉ=
^``=Z=qÜêÉçåáåÉ=
^`^=Z=qÜêÉçåáåÉ=
^`d=Z=qÜêÉçåáåÉ=
^^q=Z=^ëé~ê~ÖáåÉ=
^^`=Z=^ëé~ê~ÖáåÉ=
^^^=Z=ióëáåÉ=
^^d=Z=ióëáåÉ=
^dq=Z=pÉêáåÉ=
^d`=Z=pÉêáåÉ=
^d^=Z=^êÖáåáåÉ=
^dd=Z=^êÖáåáåÉ=
dqq=Z=s~äáåÉ=
dq`=Z=s~äáåÉ=
dq^=Z=s~äáåÉ=
dqd=Z=s~äáåÉ=
d`q=Z=^ä~åáåÉ=
d``=Z=^ä~åáåÉ=
d`^=Z=^ä~åáåÉ=
d`d=Z=^ä~åáåÉ=
d^q=Z=^ëé~êíáÅ=~ÅáÇ=
d^`=Z=^ëé~êíáÅ==~ÅáÇ=
d^^=Z=däìí~ãáÅ==~ÅáÇ=
d^d=Z=däìí~ãáÅ=~ÅáÇ=
ddq=Z=däóÅáåÉ=
dd`=Z=däóÅáåÉ=
dd^=Z=däóÅáåÉ=
ddd=Z=däóÅáåÉ=
=
Table 1 The genetic code. Nucleotides are shown as their single letter code and the amino acid each triplet codes for is shown to the right. The genetic code is conserved between different species. A gene coding for a human protein can therefore be transferred to a bacterium and still be correctly translated.
=
mêçíÉáåë=~êÉ=ÜçïÉîÉê=åçí=àìëí=~=äáåÉ~ê=ÅÜ~áå=çÑ=~ãáåç=~ÅáÇëI=íÜÉó=~êÉ=
ÑçäÇÉÇ=áåíç=ãìÅÜ=ãçêÉ=ÅçãéäÉñ=ëíêìÅíìêÉëK=qÜÉ=ëíêìÅíìê~ä=äÉîÉäë=çÑ=~=
éêçíÉáå=~êÉ=ìëì~ääó=ÇáîáÇÉÇ=áåíç=Ñçìê=Å~íÉÖçêáÉëK=qÜÉ=éêáã~êó=ëíêìÅíìêÉ=
áë=íÜÉ=ëÉèìÉåÅÉ=çÑ=~ãáåç=~ÅáÇë=áå=íÜÉ=éçäó=éÉéíáÇÉ=ÅÜ~áåI=ÅçååÉÅíÉÇ=íç=
É~ÅÜ=çíÜÉê=Äó=~=Åçî~äÉåí=éÉéíáÇÉ=ÄçåÇK=qÜÉ=ëÉÅçåÇ~êó=ëíêìÅíìêÉ=êÉÑÉêë=
íç= äçÅ~ä= ÅçåÑçêã~íáçåë= çÑ= íÜÉ= éçäó= éÉéíáÇÉ= ÅÜ~áåK= qÜÉ= íïç= ãçëí=
Åçããçå= ëÉÅçåÇ~êó= ëíêìÅíìê~ä= ÉäÉãÉåíë= ~êÉ= ~äéÜ~= ÜÉäáÅÉë= ~åÇ= ÄÉí~J ëÜÉÉíëK= qÜÉëÉ= ~êÉ= ÜÉäÇ= íçÖÉíÜÉê= Äó= ëÜçêí= ê~åÖÉ= áåíÉê~Åíáçåë= ã~áåäó=
ÅçåëáëíáåÖ= çÑ= ÜóÇêçÖÉå= ÄçåÇëK= eçï= íÜÉëÉ= ëÉÅçåÇ~êó= ëíêìÅíìê~ä=
ÉäÉãÉåíë=~êÉ=~êê~åÖÉÇ=áå=íÜêÉÉ=ÇáãÉåëáçå~ä=ëé~ÅÉ=áë=íÉêãÉÇ=íÜÉ=íÉêíá~êó=
ëíêìÅíìêÉ=çê=ÑçäÇK=qÜÉ=ä~ëí=äÉîÉä=çÑ=ëíêìÅíìê~ä=~êê~åÖÉãÉåí=áå=~=éêçíÉáå=
áë= íÜÉ= èì~íÉêå~êó= ëíêìÅíìêÉ= ïÜáÅÜ= ÇÉëÅêáÄÉë= Üçï= ëÉîÉê~ä= éçäóéÉéíáÇÉ=
ÅÜ~áåë=Å~å=áåíÉê~Åí=~åÇ=Ñçêã=~=Ñáå~ä=ãìäíáJëìÄìåáí=éêçíÉáåK==
= NM
^åçíÜÉê= íóéÉ= çÑ= ëíêìÅíìê~ä= ÉäÉãÉåí= ïáíÜáå= ~= éêçíÉáå= ~êÉ= Ççã~áåëK= ^=
ëíêìÅíìê~ä=Ççã~áå=áë=~=ëíêìÅíìê~ä=ÉäÉãÉåí=íÜ~í=Å~å=ÑçäÇ=áåÇÉéÉåÇÉåíäó=
~åÇ= áë= ëÉäÑ= ëí~ÄáäáòáåÖK= píêìÅíìê~ä= Ççã~áåë= Åçåëáëí= çå= ~îÉê~ÖÉ= çÑ= NMM=
~ãáåç= ~ÅáÇë= ~åÇ= ~êÉ= îÉêó= ëÉäÇçã= ä~êÖÉê= íÜ~å= PMM= ~ãáåç= ~ÅáÇë= xQzK=
pÉîÉê~ä=ëíêìÅíìê~ä=Ççã~áåë=~êÉ=ìëì~ääó=ÅçãÄáåÉÇ=Äó=ÑäÉñáÄäÉ=äáåâÉêë=íç=
Ñçêã= íÜÉ= Ñáå~ä= íÜêÉÉ= ÇáãÉåëáçå~ä= ëíêìÅíìêÉ= çÑ= íÜÉ= éêçíÉáåK= ^= éêçíÉáå=
Ççã~áå= áë= íóéáÅ~ääó= ~ëëçÅá~íÉÇ= ïáíÜ= ~= ëéÉÅáÑáÅ= ÑìåÅíáçå= ÉKÖK= ~å=
Éåòóã~íáÅ=~Åíáîáíó=çê=ëéÉÅáÑáÅ=áåíÉê~Åíáçå=éêçéÉêíáÉëK==
_ÉíïÉÉå= íÜÉ= ÇáÑÑÉêÉåí= âáåÖÇçãë= çÑ= äáÑÉ= íÜÉêÉ= áë= ~= ÇáÑÑÉêÉåÅÉ= áå= íÜÉ=
~îÉê~ÖÉ= åìãÄÉê= çÑ= Ççã~áåë= éÉê= éêçíÉáåK= cçê= áåëí~åÅÉI= Éìâ~êóçíáÅ=
éêçíÉáåë=Ü~îÉ=çå=~îÉê~ÖÉ=~=ä~êÖÉê=åìãÄÉê=çÑ=Ççã~áåë=éÉê=éêçíÉáå=íÜ~å=
íÜçëÉ=Ñêçã=éêçâ~êóçíÉë=xRzK=eçïÉîÉêI=íÜÉ=ãÉÇá~å=ëáòÉ=çÑ=íÜÉ=Ççã~áåë=
~êÉ=ëìêéêáëáåÖäó=ëáãáä~ê=ÄÉíïÉÉå=íÜÉ=ÇáÑÑÉêÉåí=éÜóäçÖÉåíáÅ=Öêçìéë=xRzK==
=
A Historical Perspective
Cloning and Protein Production
ré= ìåíáä= ãáÇ= NVTMëI= íÜÉ= çåäó= ~î~áä~ÄäÉ= çéíáçå= íç= çÄí~áå= éêçíÉáå= Ñçê=
ÄáçÅÜÉãáÅ~ä= ëíìÇáÉë= ï~ë= Ñêçã= íÜÉ= å~íáîÉ= ëçìêÅÉK= få= íÜÉ= ÄÉÖáååáåÖ= çÑ=
NVTMë=íÜÉ=ÄáçíÉÅÜåçäçÖó=êÉîçäìíáçå=ëí~êíÉÇ=~åÇ=çåÉ=çÑ=íÜÉ=ãáäÉëíçåÉë=
ï~ë=íÜÉ=éìêáÑáÅ~íáçå=~åÇ=ÅÜ~ê~ÅíÉêáò~íáçå=çÑ=~=êÉëíêáÅíáçå=ÉåòóãÉ=Ñêçã=
eÉãçéÜáäìë= áåÑäìÉåò~É= xSI= TzK= qÜÉëÉ= êÉëíêáÅíáçå= ÉåòóãÉë= Éå~ÄäÉÇ=
ëÅáÉåíáëíë= íç= Åìí= çìí= ak^= éáÉÅÉë= Ñêçã= ÖÉåçãáÅ= ak^= ~í= ëéÉÅáÑáÅ=
éçëáíáçåëK=^å=Éèì~ääó=áãéçêí~åí=ÇáëÅçîÉêó=ï~ë=íÜÉ=áëçä~íáçå=çÑ=äáÖ~ëÉë=
ïÜáÅÜ= ~ääçïÉÇ= íÜÉ= àçáåáåÖ= çÑ= ak^= Ñê~ÖãÉåíë= xUI= VzK= ^åçíÜÉê=
ãáäÉëíçåÉ=ï~ë=íÜÉ=ÅçåëíêìÅíáçå=çÑ=íÜÉ=Ñáêëí=~êíáÑáÅá~ä=éä~ëãáÇ=Äó=`çÜÉå=
~åÇ= ÅçJïçêâÉêë= áå= NVTO= xNMz= ïÜáÅÜ= ~ääçïÉÇ= íÜÉ= íê~åëÑÉê= çÑ= ÖÉåÉíáÅ=
ã~íÉêá~ä= ÄÉíïÉÉå= çêÖ~åáëãëK= qÜáë= äÉÇ= íç= íÜÉ= ÅäçåáåÖ= çÑ= ëÉîÉê~ä= ÖÉåÉ=
Ñê~ÖãÉåíë= Ñêçã= ÇáÑÑÉêÉåí= éêçâ~êóçíáÅ= ~åÇ= Éìâ~êóçíáÅ= çêÖ~åáëãë= xNNI=
NOzK= = få= íÜÉ= ä~íÉ= NVTMë= íÜÉ= Ñáêëí= Éñ~ãéäÉë= çÑ= çîÉêÉñéêÉëëáçå= çÑ=
Éìâ~êóçíáÅ= éÉéíáÇÉë= ïÉêÉ= êÉéçêíÉÇK= få= NVTT= íÜÉ= Üìã~å= ÜçêãçåÉ=
ëçã~íçëí~íáå=ï~ë=éêçÇìÅÉÇ=áå=bK=Åçäá=xNPz=~åÇ=íïç=óÉ~êë=ä~íÉê=Üìã~å=
áåëìäáå= xNQz= ~åÇ= Üìã~å=ÖêçïíÜ=ÜçêãçåÉ=xNRz=ïÉêÉ=éêçÇìÅÉÇK=qÜÉëÉ=
éáçåÉÉêáåÖ=ÉÑÑçêíë=éêçîÉÇ=íÜ~í=Éìâ~êóçíáÅ=éêçíÉáåë=~åÇ=éÉéíáÇÉë=ÅçìäÇ=
ÄÉ=éêçÇìÅÉÇ=áå=bK=ÅçäáK=få=NVUO=êÉÅçãÄáå~åí=áåëìäáå=ï~ë=~ééêçîÉÇ=Äó=
= NN
íÜÉ=rp=cççÇ=C=aêìÖ=^Çãáåáëíê~íáçå=~ë=íÜÉ=Ñáêëí=ÖÉåÉíáÅ~ääó=ÉåÖáåÉÉêÉÇ=
ÇêìÖ=xNSzK==
fí= ï~ë= ÜçïÉîÉê= èìáÅâäó= êÉ~äáòÉÇ= íÜ~í= áå= ã~åó= Å~ëÉë= íÜÉ= êÉÅçãÄáå~åí=
éêçíÉáå= ï~ë= åçí= ÑçäÇÉÇ= ÅçêêÉÅíäó= áå= íÜÉ= ÅÉääI= ~åÇ= áåëíÉ~Ç= áåÅäìëáçå=
ÄçÇáÉë=ïÉêÉ=éêçÇìÅÉÇK=fí=Ü~Ç=éêÉîáçìëäó=ÄÉÉå=çÄëÉêîÉÇ=íÜ~í=~Äåçêã~ä=
bK= Åçäá= éêçíÉáåë= ÅçìäÇ= ~ÅÅìãìä~íÉ= áå= íÜÉëÉ= ~ÖÖêÉÖ~íÉë= xNTI= NUzK= qÜÉ=
éêçÇìÅíáçå= çÑ= áåÅäìëáçå= ÄçÇáÉë= ï~ë= åçí= ÉåíáêÉäó= ÇÉéÉåÇÉåí= çå= íÜÉ=
Éìâ~êóçíáÅ=çêáÖáå=çÑ=íÜÉ=êÉÅçãÄáå~åí=éêçíÉáå=ëáåÅÉ=áí=Ü~Ç=ÄÉÉå=ëÜçïå=
íÜ~í=bK=Åçäá=éêçíÉáåë=ÉñéêÉëëÉÇ=~í=ÜáÖÜ=äÉîÉäë=~äëç=ÉåÇÉÇ=ìé=áå=áåÅäìëáçå=
ÄçÇáÉëK= fí= ï~ë= ~äëç= êÉ~äáòÉÇ= íÜ~í= Äó= ÑìëáåÖ= íÜÉ= éêçíÉáå= çê= éÉéíáÇÉ= çÑ=
áåíÉêÉëí=íç=~=Ä~ÅíÉêá~ä=éêçíÉáåI=íÜÉ=~ãçìåí=çÑ=ã~íÉêá~ä=íÜ~í=ï~ë=ÑçìåÇ=
áå=íÜÉ=ëçäìÄäÉ=Ñê~Åíáçå=ÅçìäÇ=ÄÉ=áåÅêÉ~ëÉÇK=
qÜÉ=êÉ~ëçåë=ïÜó=áåÅäìëáçå=ÄçÇáÉë=~êÉ=éêçÇìÅÉÇ=ìéçå=çîÉêÉñéêÉëëáçå=
~êÉ=ëçãÉïÜ~í=ÅäÉ~êÉê=íçÇ~ó=~åÇ=ïáää=ÄÉ=ÇáëÅìëëÉÇ=ÄÉäçïK=
=
få=NVUR=íÜÉ=éçäóãÉê~ëÉ=ÅÜ~áå=êÉ~Åíáçå=Em`oF=ãÉíÜçÇ=ï~ë=ÇÉëÅêáÄÉÇI=
ïÜáÅÜ=êÉîçäìíáçåáòÉÇ=íÜÉ=ÑáÉäÇ=çÑ=ãçäÉÅìä~ê=ÄáçäçÖó=xNVzK=m`o=ã~ÇÉ=áí=
éçëëáÄäÉ=íç=~ãéäáÑó=ak^=Ñêçã=îÉêó=ëã~ää=~ãçìåíë=çÑ=ëí~êíáåÖ=ã~íÉêá~ä=
~åÇ= áí= ëáãéäáÑáÉÇ= íÜÉ= éêçÅÉëë= çÑ= ÅäçåáåÖ= áããÉåëÉäóK= qÜÉ= áåîÉåíáçå= çÑ=
íÜÉ=m`o=ãÉíÜçÇ=ï~ë=~ï~êÇÉÇ=íÜÉ=kçÄÉä=mêáòÉ=áå=`ÜÉãáëíêó=áå=NVVPK=
qÜÉêÉ=ï~ë=~äëç=~=ê~éáÇ=áãéêçîÉãÉåí=çÑ=ÉñéêÉëëáçå=îÉÅíçêë=~åÇ=çåÉ=çÑ=
íÜÉ= ä~êÖÉëí= ~Çî~åÅÉë= ï~ë= ã~ÇÉ= áå= NVUS= Äó= píìÇáÉê= ~åÇ= jçÑÑ~ííK=
píìÇáÉê= ~åÇ= jçÑÑ~íí= ÇÉëÅêáÄÉÇ= ~å= ÉñéêÉëëáçå= ëóëíÉã= íÜ~í= ìëÉÇ= íÜÉ=
Ä~ÅíÉêáçéÜ~ÖÉ= qT= éêçãçíÉê= íç= ÇêáîÉ= íÜÉ=íê~åëÅêáéíáçå= çÑ= ok^= = xOMzK=
sÉêó=ÜáÖÜ=äÉîÉäë=çÑ=éêçíÉáåI=ìé=íç=RMB=çÑ=íÜÉ=íçí~ä=~ãçìåí=çÑ=éêçíÉáå=
áå= íÜÉ= bK= Åçäá= ÅÉääI= ÅçìäÇ= ÄÉ= éêçÇìÅÉÇK= qÜÉ= ëóëíÉã= ~äëç= éêçîáÇÉÇ= ~=
íáÖÜíÉê=Åçåíêçä=çÑ=íê~åëÅêáéíáçåK=qÜÉ=qT=Ä~ëÉÇ=ëóëíÉã=áë=ëíáää=íÜÉ=ãçëí=
ïáÇÉäó= ìëÉÇ= ëóëíÉã= Ñçê= çîÉêÉñéêÉëëáçå= çÑ= éêçíÉáåë= áå= bK= ÅçäáI= ÑìêíÜÉê=
ÇÉãçåëíê~íáåÖ= íÜÉ= ÖêÉ~í= áãéçêí~åÅÉ= çÑ= íÜáë= áåîÉåíáçåI= ïÜáÅÜ= ïáää= ÄÉ=
ÇáëÅìëëÉÇ=ä~íÉêK==
=
bîÉå=íÜçìÖÜ=íÜÉ=éêçÇìÅíáçå=çÑ=êÉÅçãÄáå~åí=éêçíÉáåë=ï~ë=ÄÉÅçãáåÖ=~=
ëí~åÇ~êÇ=íÉÅÜåáèìÉI=éìêáÑáÅ~íáçå=çÑ=íÜÉ=çîÉêÉñéêÉëëÉÇ=éêçíÉáå=ï~ë=ëíáää=
Ñ~áêäó= ä~ÄçêáçìëK= qÜÉ= Ñáêëí= éìêáÑáÅ~íáçå= í~Ö= ï~ë= ÇÉëÅêáÄÉÇ= áå= NVUP= Äó=
rÜä¨å= Éí= ~äK= xONzK= qÜÉ= ëí~éÜóäçÅçÅÅ~ä= éêçíÉáå= ^= ï~ë= ÑìëÉÇ= íç= íÜÉ=
= NO
éêçíÉáå=çÑ=áåíÉêÉëí=~åÇ=íÜÉ=~ÑÑáåáíó=çÑ=éêçíÉáå=^=íç=fÖd=ï~ë=ìíáäáòÉÇ=íç=
Å~éíìêÉ= íÜÉ= ÜóÄêáÇ= éêçíÉáåK= qÜÉ= éìêáÑáÅ~íáçå= í~Ö= íÜ~í= áë= ãçëí= ïáÇÉäó=
ìëÉÇ= íçÇ~ó= ï~ë= Ñáêëí= ÇÉëÅêáÄÉÇ= áå= NVUU= xOOzK= qÜÉ= ãÉíÜçÇ= ìíáäáòÉë= ~=
êÉëáå=ïáíÜ=áããçÄáäáòÉÇ=káOH=áçåë=íç=ïÜáÅÜ=ÜáëíáÇáåÉ=êÉëáÇìÉë=ÄáåÇ=ïáíÜ=
~= îÉêó= ÜáÖÜ= ëÉäÉÅíáîáíóK= eçÅÜìäá= ~åÇ= ÅçJïçêâÉêë= ÅêÉ~íÉÇ= ~= îÉÅíçê=
Åçåí~áåáåÖ=ëáñ=ÅçåëÉÅìíáîÉ=ÜáëíáÇáåÉ=ÅçÇçåëI=~ÑíÉê=ïÜáÅÜ=íÜÉ=éêçíÉáå=çÑ=
áåíÉêÉëí= ï~ë= ÅäçåÉÇK= qÜáë= áåîÉåíáçå= ÅçãéäÉíÉäó= êÉîçäìíáçåáòÉÇ= íÜÉ=
éìêáÑáÅ~íáçå=çÑ=êÉÅçãÄáå~åí=éêçíÉáåë=~åÇ=Ü~ë=Éå~ÄäÉÇ=íÜÉ=éìêáÑáÅ~íáçå=
çÑ= éêçíÉáåë= çå= ~= ëÅ~äÉ= íÜ~í= ïçìäÇ= åçí= Ü~îÉ= ÄÉÉå= áã~ÖáåÉÇ= OM= óÉ~êë=
~ÖçK= qçÇ~ó= íÜáë= ãÉíÜçÇ= áë= êÉÑÉêêÉÇ= íç= ~ë= áããçÄáäáòÉÇ= ãÉí~ä= ~ÑÑáåáíó=
ÅÜêçã~íçÖê~éÜó=Efj^`FK==
=
Structural Biology
qÜÉ= ÑçìåÇ~íáçåë= çÑ= ãçÇÉêå= ëíêìÅíìê~ä= ÄáçäçÖó= ïÉêÉ= ä~áÇ= áå= íÜÉ= É~êäó=
OMíÜ=ÅÉåíìêó=Äó=~=åìãÄÉê=çÑ=ÇáëíáåÖìáëÜ=êÉëÉ~êÅÜÉêëK=táäÜÉäã=`çåê~Ç=
o∏åíÖÉå=EkçÄÉä=éêáòÉ=ä~ìêÉ~íÉ=NVMNF=ÇáëÅçîÉêÉÇ=uJê~ó=ê~Çá~íáçå=~åÇ=
j~ñ= îçå= i~ìÉ= EkçÄÉä= éêáòÉ= ä~ìêÉ~íÉ= NVNQF= ÇáëÅçîÉêÉÇ= íÜ~í= Åêóëí~äë=
ÇáÑÑê~ÅíÉÇ= uJê~óëK= c~íÜÉê= ~åÇ= ëçåI= páê= táääá~ã= eÉåêó= _ê~ÖÖ= ~åÇ=
táääá~ã= i~ïêÉåÅÉ= _ê~ÖÖI= éáçåÉÉêÉÇ= ÉÑÑçêíë= áå= íÜÉ= ~å~äóëáë= çÑ= Åêóëí~ä=
ëíêìÅíìêÉë=Äó=uJê~ó=ÇáÑÑê~ÅíáçåI=~åÇ=ïÉêÉ=~ï~êÇÉÇ=íÜÉ=kçÄÉä=mêáòÉ=áå=
mÜóëáÅë=áå=NVNRK=
få=NVPT=j~ñ=mÉêìíò=ã~ÇÉ=íÜÉ=Ñáêëí=ÉñéÉêáãÉåíë=íç=áåîÉëíáÖ~íÉ=áÑ=áí=ï~ë=
éçëëáÄäÉ= íç= ÇÉíÉêãáåÉ= íÜÉ= ëíêìÅíìêÉ= çÑ= íÜÉ= éêçíÉáå= ÜÉãçÖäçÄáå= Äó= uJ ê~ó=ÇáÑÑê~ÅíáçåK=qÉå=óÉ~êë=ä~íÉêI=gçÜå=hÉåÇêÉï=àçáåÉÇ=j~ñ=mÉêìíò=ä~Ä=
~åÇ= ~äíÜçìÖÜ= ÅçåëáÇÉê~ÄäÉ= ÉÑÑçêíë= ïÉêÉ=ã~ÇÉI= áí= ï~ë= åçí= ìåíáä= NVRPI=
Äó= ìëáåÖ= íÜÉ= ~ÇÇáíáçå= çÑ= ãÉêÅìêó= íç= íÜÉ= Åêóëí~äëI= íÜ~í= íÜÉ=
Åêóëí~ääçÖê~éÜáÅ= éÜ~ëÉë= ÅçìäÇ= ÄÉ= çÄí~áåÉÇK= ^ÑíÉê= OO= óÉ~êë= çÑ= ÜÉêçáÅ=
ÉÑÑçêíë=íÜÉ=Ñáêëí=éêçíÉáå=ëíêìÅíìêÉ=ï~ë=éìÄäáëÜÉÇ=Äó=hÉåÇêÉï= Éí=~äK=áå=
NVRU= xOPzK= qÜÉ= ëíêìÅíìêÉ= ï~ë= çÑ= ëéÉêã= ïÜ~äÉ= ãóçÖäçÄáå= ~åÇ= íç= ~=
êÉëçäìíáçå= çÑ= S= üåÖëíê∏ã= EüFK= qÜáë= ëíêìÅíìêÉ= ï~ë= ÑçääçïÉÇ= Äó= ~=
ëíêìÅíìêÉ= çÑ= Ü~ÉãçÖäçÄáå= áå= NVSP= Äó= jìáêÜÉ~Ç= ~åÇ= mÉêìíò= íç= ~=
êÉëçäìíáçå=çÑ=RKR=ü=xOQzK=_çíÜ=mÉêìíò=~åÇ=hÉåÇêÉï=êÉÅÉáîÉÇ=íÜÉ=kçÄÉä=
mêáòÉ=áå=`ÜÉãáëíêó=áå=NVSP=Ñçê=íÜÉáê=ÖêÉ~í=ÅçåíêáÄìíáçåë=íç=íÜÉ=ÑáÉäÇ=çÑ=
ëíêìÅíìê~ä=ÄáçäçÖóK=få=NVTN=íÜÉ=éêçíÉáå=Ç~í~=Ä~åâ=Ema_F=ï~ë=ÅêÉ~íÉÇ=
~ë=~=êÉéçëáíçêó=çÑ=~ää=éìÄäáÅäó=êÉäÉ~ëÉÇ=ã~ÅêçãçäÉÅìä~ê=ëíêìÅíìêÉë=xORzK=
= NP
qçÇ~ó=íÜÉ=ma_=Åçåí~áåë=ãçêÉ=íÜ~å=PRIMMM=éêçíÉáå=ëíêìÅíìêÉë=EcáÖìêÉ=
NFI= ~åÇ=ã~åó= çÑ=íÜÉ= ëíêìÅíìêÉë= Ü~îÉ=~= êÉëçäìíáçå=Ñ~ê=ÉñÅÉÉÇáåÖ= íÜçëÉ=
áåáíá~ä= ÜÉãçÖäçÄáå= ~åÇ= ãóçÖäçÄáå= ëíêìÅíìêÉëK= qÜÉ= ma_= Ç~í~Ä~ëÉ= Å~å=
íçÇ~ó=ÄÉ=~ÅÅÉëëÉÇ=îá~=áåíÉêåÉíOK=
låÉ=çÑ=íÜÉ=åÉñí=ÄáÖ=ÇÉîÉäçéãÉåíë=áå=íÜÉ=ÑáÉäÇ=çÑ=uJê~ó=Åêóëí~ääçÖê~éÜó=
ï~ë= íÜÉ= ìëÉ= çÑ= ÅêóçJÅççäáåÖ= ~åÇ= Ñä~ëÜ= ÑêÉÉòáåÖ= çÑ= Åêóëí~äë= áå= íÜÉ=
ÄÉÖáååáåÖ= çÑ= íÜÉ= NVVMëK= qÜÉ= áåíêçÇìÅíáçå= çÑ= åÉï= éÜ~ëáåÖ= ãÉíÜçÇë=
ëìÅÜ= ~ë= ãìäíáï~îÉäÉåÖíÜ= ~åçã~äçìë= ÇáÑÑê~Åíáçå= Ej^aF= çê= ëáåÖäÉ=
ï~îÉäÉåÖíÜ=~åçã~äçìë=ÇáÑÑê~Åíáçå=Ep^aF=Ü~îÉ=~äëç=ÅçåíêáÄìíÉÇ=ÖêÉ~íäó=
íç= íÜÉ= ~äãçëí= ÉñéçåÉåíá~ä= áåÅêÉ~ëÉ= áå= éêçíÉáå= ëíêìÅíìêÉë= ÇÉéçëáíÉÇ= áå=
íÜÉ=ma_=EcáÖìêÉ=NFK=
=
0 10000 20000 30000 40000
1973 1975
1977 1979
1981 1983
1985 1987
1989 1991
1993 1995
1997 1999
2001 2003
2005 Year
Number of Structures
Deposited structures for the year Total available structures
=
Figure 1 Number of structures deposited in the Protein Data Bank. Data obtained from the PDB website.
=
Membrane Proteins
^ää=äáîáåÖ=ÅÉääë=~êÉ=ëìêêçìåÇÉÇ=Äó=~=íÜáå=ãÉãÄê~åÉ=ÅçãéçëÉÇ=çÑ=äáéáÇëK=
qÜÉêÉ= Ü~îÉ= ÄÉÉå= ëÉîÉê~ä= ÇáÑÑÉêÉåí= ãçÇÉäë= çÑ= Üçï= íÜáë= ãÉãÄê~åÉ= áë=
çêÖ~åáòÉÇK=få=NVPR=a~åáÉääá=~åÇ=a~îëçå=ëìÖÖÉëíÉÇ=~=ãçÇÉä=ïÜÉêÉ=íÜÉ=
äáéáÇë= ~êÉ= çêÖ~åáòÉÇ= áå= ~= Äáä~óÉê= ëìêêçìåÇÉÇ= Äó= ~= éêçíÉáå= ä~óÉê===
=========================================
O=ÜííéWLLïïïKéÇÄKçêÖ=
= NQ
EcáÖìêÉ= OFK= få= NVTO= páåÖÉê= ~åÇ= káÅÜçäëçå= éêçéçëÉÇ= íÜÉ= ÑäìáÇ= ãçë~áÅ=
ãçÇÉäI=ïÜáÅÜ=ïáíÜ=ëçãÉ=ãçÇáÑáÅ~íáçåëI=áë=ëíáää=íçÇ~ó=íÜÉ=ãçÇÉä=ìëÉÇ=íç=
ÇÉëÅêáÄÉ= ÄáçäçÖáÅ~ä= ãÉãÄê~åÉë= xOSzK= qÜáë= ãçÇÉä= êÉí~áåë= íÜÉ= äáéáÇ=
Äáä~óÉêI= Äìí= íÜÉ= éêçíÉáåJäáéáÇJéêçíÉáå= ë~åÇïáÅÜ= ï~ë= êÉéä~ÅÉÇ= Äó= ~=
ãçÇÉä=ïÜÉêÉ=íÜÉ=éêçíÉáåë=“Ñäç~íÒ=áå=íÜÉ=ãÉãÄê~åÉ=EcáÖìêÉ=OFK==
=
Danielli and Davson 1935 Singer and Nicolson 1972
Protein Integral protein
Peripheral protein
a b
=
Figure 2 Schematic outline of the different lipid bilayer models. (A) The model suggested by Danelli and Davson. In this model the lipid is organised in a bilayer surrounded by a protein layer. (B) The fluid mosaic model suggested by Singa and Nicolson. The lipids are arranged in bilayer but the proteins can span the bilayer.
=
jÉãÄê~åÉ= éêçíÉáåë= ÅçåëíáíìíÉ= ÄÉíïÉÉå= OMJPM= B= çÑ= ~ää= çéÉå= êÉ~ÇáåÖ=
Ñê~ãÉëI=ÇÉéÉåÇáåÖ=çå=íÜÉ=çêÖ~åáëã=xOTzK=jÉãÄê~åÉ=éêçíÉáåë=~äëç=éä~ó=
ÅêìÅá~ä= êçäÉë= áå= ã~åó= ÄáçäçÖáÅ~ä= éêçÅÉëëÉëI= Äìí= Åçãé~êÉÇ= íç= íÜÉáê=
ëçäìÄäÉ=é~êíåÉêëI=êÉä~íáîÉäó=äáííäÉ=áë=âåçïå=~Äçìí=íÜÉáê=ëíêìÅíìêÉ=~í=íÜÉ=
~íçãáÅ=äÉîÉäK==
qÜáë=áë=ÇìÉ=íç=íÜÉ=ìåé~ê~ääÉäÉÇ=ÇáÑÑáÅìäíáÉë=ÉåÅçìåíÉêÉÇ=ïÜÉå=íêóáåÖ=íç=
çîÉêÉñéêÉëëI=éìêáÑóI=~åÇ=Åêóëí~ääáòÉ=ãÉãÄê~åÉ=éêçíÉáåëK==
qÜÉ=Ñáêëí=ãÉãÄê~åÉ=éêçíÉáå=ëíêìÅíìêÉ=ÇÉíÉêãáåÉÇ=~í=~íçãáÅ=êÉëçäìíáçå=
ï~ë=íÜÉ=éÜçíçëóåíÜÉíáÅ=êÉ~Åíáçå=ÅÉåíêÉ=çÑ=oÜçÇçéëÉìÇçãçå~ë=îáêáÇáë=
xOUzK=qÜáë=~ÅÜáÉîÉãÉåí=ï~ë=~ï~êÇÉÇ=íÜÉ=kçÄÉä=mêáòÉ=áå=`ÜÉãáëíêó=áå=
NVUUK= páåÅÉ= NVURI= ïÜÉå= íÜÉ= éÜçíçëóåíÜÉíáÅ= êÉ~Åíáçå= ÅÉåíêÉ= ï~ë=
éìÄäáëÜÉÇI= VT= ~ÇÇáíáçå~ä= ìåáèìÉ= ãÉãÄê~åÉ= éêçíÉáå= ëíêìÅíìêÉë= Ü~îÉ=
ÄÉÉå=ëçäîÉÇPK==
=========================================
P=ÜííéWLLÄä~åÅçKÄáçãçäKìÅáKÉÇìLjÉãÄê~åÉ|mêçíÉáåë|ñí~äKÜíãä=
= NR
`çãé~êÉÇ=íç=ëçäìÄäÉ=éêçíÉáåëI=~=îÉêó=ä~êÖÉ=Ñê~Åíáçå=çÑ=íÜÉ=ÇÉíÉêãáåÉÇ=
ãÉãÄê~åÉ= éêçíÉáå= ëíêìÅíìêÉë= Ü~îÉ= ÄÉÉå= áëçä~íÉÇ= Ñêçã= íÜÉáê= å~íáîÉ=
ëçìêÅÉ=xOVzK=^ãçåÖ=íÜÉ=Éìâ~êóçíáÅ=ãÉãÄê~åÉ=éêçíÉáå=ëíêìÅíìêÉëI=íÜÉêÉ=
~êÉ= çåäó= íïç= Éñ~ãéäÉë= ïÉêÉ= êÉÅçãÄáå~åí= éêçíÉáå= Ü~îÉ= ÄÉÉå= ìëÉÇ= íç=
ëçäîÉ=~=ÜáÖÜ=êÉëçäìíáçå=ëíêìÅíìêÉ=xPMI=PNzK=få=íÜÉëÉ=íïç=Å~ëÉëI=bK=Åçäá=
ï~ë= åçí= ìëÉÇ= Ñçê= ÉñéêÉëëáçå= Äìí= áåëíÉ~Ç= Éìâ~êóçíáÅ= Üçëíë= ïÉêÉ= ìëÉÇK=
qÜÉ= éêçÄäÉãë= ÉåÅçìåíÉêÉÇ= ïÜÉå= íêóáåÖ= íç= çîÉêÉñéêÉëë= ãÉãÄê~åÉ=
éêçíÉáåë=ïáää=ÄÉ=ÇáëÅìëëÉÇ=áå=ãçêÉ=ÇÉí~áä=ÄÉäçïK==
=
Structural Genomics
få= NVTR= p~åÖÉê= ~åÇ= `çìäëçå= éìÄäáëÜÉÇ= íÜÉ= ãÉíÜçÇ= íÜ~í= äÉÇ= íç= ~=
êÉîçäìíáçå= áå= ak^= ëÉèìÉåÅáåÖ= íÉÅÜåçäçÖó= xPOzK= få= NVTT= p~åÖÉê= ~åÇ=
ÅçääÉ~ÖìÉë= éêÉëÉåíÉÇ= íÜÉ= Ñáêëí= ÅçãéäÉíÉ= ak^= ëÉèìÉåÅÉ= çÑ= íÜÉ=
Ä~ÅíÉêáçéÜ~ÖÉ= éÜáJñNTQ= xPPzK= qÜÉ= Ñáêëí= çêÖ~åáëã= íç= ÄÉ= ÅçãéäÉíÉäó=
ëÉèìÉåÅÉÇ= ï~ë= íÜÉ= Ä~ÅíÉêáìã= e~ÉãçéÜáäìë= áåÑäìÉåò~É= xPQzK= qÜÉ=
ãÉíÜçÇ= ìëÉÇ= íç= ëÉèìÉåÅÉ= eK= áåÑäìÉåò~É= ï~ë= Ä~ëÉÇ= çå= ê~åÇçãäó=
ëÉèìÉåÅáåÖ= íÜÉ= ïÜçäÉ= ÖÉåçãÉ= ÑçääçïÉÇ= Äó= ~ëëÉãÄäó= çÑ= íÜÉ= ê~åÇçã=
ëÉèìÉåÅÉÇ=Ñê~ÖãÉåíëK=qÜáë=~ééêç~ÅÜI=Å~ääÉÇ=ëÜçíÖìå=ëÉèìÉåÅáåÖI=ï~ë=
~äëç=ìëÉÇ=ïÜÉå=íÜÉ=Üìã~å=ÖÉåçãÉ=ï~ë=ëÉèìÉåÅÉÇ=~í=íÜÉ=ÄÉÖáååáåÖ=çÑ=
íÜáë= ÅÉåíìêó= xPRI= PSzK= qç= Ç~íÉI= ãçêÉ= íÜ~å= OUM= éêçâ~êóçíáÅ= ~åÇ= QM=
Éìâ~êóçíáÅ= ÖÉåçãÉë= Ü~îÉ= ÄÉÉå= ÅçãéäÉíÉäó= ëÉèìÉåÅÉÇQ= ~åÇ= áå= íçí~äI=
çîÉê= NMM= Äáääáçå= Ä~ëÉë= Ñêçã= ãçêÉ= íÜ~å= NSRIMMM= çêÖ~åáëãë= Å~å= ÄÉ=
ÑçìåÇ=áå=ëÉèìÉåÅÉ=Ç~í~Ä~ëÉë=ïçêäÇïáÇÉK==
qÜÉ=ÑáÉäÇ=çÑ=ÖÉåçãáÅë=Ü~ë=êÉîçäìíáçåáòÉÇ=íÜÉ=ï~ó=ÄáçäçÖáÅ~ä=ëÅáÉåÅÉ=áë=
ÇçåÉK= qçÇ~ó= áí= áë= í~âÉå= Ñçê= Öê~åíÉÇ= íÜ~í= íÜÉëÉ= ÜìÖÉ= Ç~í~Ä~ëÉë= ~êÉ=
~î~áä~ÄäÉ= íç= ëÉ~êÅÜ= Ñçê= ÅäìÉë= ~Äçìí= íÜÉ= ÑìåÅíáçåë= çÑ= åçîÉä= éêçíÉáåëK=
kÉï=ÑáÉäÇë=çÑ=ÄáçäçÖó=íÜ~í=ïçìäÇ=åçí=Ü~îÉ=ÉñáëíÉÇ=çåäó=NR=óÉ~êë=~Öç=
Ü~îÉ= ÉãÉêÖÉÇI= áKÉK= ÄáçáåÑçêã~íáÅëK= eçïÉîÉêI= íç= ìåÇÉêëí~åÇ= ãçëí=
ÄáçäçÖáÅ~ä=éêçÅÉëëÉë=áå=ÇÉí~áäI=çåÉ=Ü~ë=íç=ëíìÇó=íÜÉ=éêçíÉáåëK=qÜÉ=ÑáÉäÇ=
çÑ=éêçíÉçãáÅë=ÉãÉêÖÉÇ=ïÜÉå=íÜÉ=Ñáêëí=ÖÉåçãÉë=ïÉêÉ=ÅçãéäÉíÉÇ=~åÇ=áå=
NVVU=íÜÉ=ÑáÉäÇ=çÑ=ëíêìÅíìê~ä=ÖÉåçãáÅë=ï~ë=ëí~êíáåÖ=íç=í~âÉ=ëÜ~éÉ=xPTzK=
fí= ï~ë= èìáÅâäó= êÉ~äáòÉÇ= íÜ~í= çåÉ= çÑ= íÜÉ= ã~áå= éêçÄäÉãë= áå= ëíêìÅíìê~ä=
ÖÉåçãáÅë= ï~ë= íÜÉ= éêçÇìÅíáçå= çÑ= ëìáí~ÄäÉ= éêçíÉáå= ë~ãéäÉë= xPUzK=
=========================================
Q=ÜííéWLLïïïKÖÉåçãÉëçåäáåÉKçêÖ=
= NS
qÜÉêÉÑçêÉI=~=äçí=çÑ=íáãÉ=~åÇ=ÉÑÑçêí=Ü~ë=ÄÉÉå=éìí=áåíç=ÇÉîÉäçéáåÖ=åÉï=
ãÉíÜçÇë= íÜ~í= ïáää= áåÅêÉ~ëÉ= íÜÉ= íÜêçìÖÜéìí= çÑ= íÜÉ= éêçíÉáå= éêçÇìÅíáçå=
ëíÉéK=
qÜÉ= ÑçÅìë= çÑ= É~ÅÜ= çÑ= íÜÉ= ÇáÑÑÉêÉåí= ëíêìÅíìê~ä= ÖÉåçãáÅë= éêçÖê~ãë=
ïçêäÇïáÇÉ= ÇáÑÑÉêë= ëäáÖÜíäóK= pçãÉ= ÉÑÑçêíë= Ü~îÉ= ~= ÑçäÇJÄ~ëÉÇ= ~ééêç~ÅÜ=
íÜ~í= áë= íç= íêó= ÇÉíÉêãáåáåÖ= ~= ãÉãÄÉê= çÑ= É~ÅÜ= ÑçäÇLÇçã~áåK= líÜÉê=
éêçÖê~ãë= Ü~îÉ= ÑçÅìëÉÇ= çå= é~íÜçÖÉåáÅ= çêÖ~åáëãëK= tÜ~í= ~ää= çÑ= íÜÉëÉ=
ÉÑÑçêíë= Ü~îÉ= áå= Åçããçå= áë= íÜ~í= ÉîÉêó= ëíÉé= áå= íÜÉ= éêçÅÉëë= Ü~ë= ÄÉÉå=
çéíáãáòÉÇ= íç= ~ÅÜáÉîÉ= ~ë= ÜáÖÜ= ~= íÜêçìÖÜéìí= ~ë= éçëëáÄäÉK= qç= Ç~íÉ=
ëíêìÅíìê~ä=ÖÉåçãáÅë=éêçàÉÅíë=ïçêäÇïáÇÉ=Ü~îÉ=ÇçåÉ=ÉñéÉêáãÉåíë=çå=~å=
ìåé~ê~ääÉäÉÇ= ëÅ~äÉI= ~åÇ= Ü~îÉ= ÅäçåÉÇ= ãçêÉ= íÜ~å= RUIMMM= ÖÉåÉë= ~åÇ=
ëÅêÉÉåÉÇ=ãçêÉ=íÜ~å=PPIMMM=ÖÉåÉë=Ñçê=ÉñéêÉëëáçåRK==
=
Protein Overexpression
^ë=ãÉåíáçåÉÇ=É~êäáÉêI=íÜÉ=éêçÇìÅíáçå=çÑ=ëìáí~ÄäÉ=éêçíÉáå=ë~ãéäÉë=áë=~=
äáãáíáåÖ= Ñ~Åíçê= áå= ã~åó= ÄáçÅÜÉãáÅ~ä= ëíìÇáÉë= ~åÇ= ÉëéÉÅá~ääó= Ñçê=
ëíêìÅíìê~ä= ëíìÇáÉëK= qÜÉ= ãçëí= Åçããçåäó= ìëÉÇ= çêÖ~åáëã= áë= bK= Åçäá= ~åÇ=
íÜÉêÉ=~êÉ=ëÉîÉê~ä=êÉ~ëçåë=ïÜó=bK=Åçäá=áë=íÜÉ=éêÉÑÉêêÉÇ=ÜçëíK=cáêëí=çÑ=~ääI=
bK=Åçäá=áë=éêçÄ~Ääó=çåÉ=çÑ=íÜÉ=ãçëí=ïÉää=ëíìÇáÉÇ=çêÖ~åáëãë=~åÇ=ã~åó=
ÑìåÇ~ãÉåí~ä=éêçéÉêíáÉë=çÑ=bK=Åçäá=ÅÉääë=Ü~îÉ=ÄÉÉå=áåîÉëíáÖ~íÉÇ=áå=ÖêÉ~í=
ÇÉí~áäK=páåÅÉ=bK=Åçäá=áë=ïÉää=ëíìÇáÉÇ=íÜÉêÉ=~êÉ=ëÉîÉê~ä=ãçäÉÅìä~ê=ÄáçäçÖó=
íççäë=~î~áä~ÄäÉ=Ñçê=ìëÉ=ïáíÜ=bK=ÅçäáK=^åçíÜÉê=êÉ~ëçå=íÜ~í=ã~âÉë=bK=Åçäá=
ëìÅÜ=~å=~ííê~ÅíáîÉ=Üçëí=~êÉ=íÜÉ=éçëëáÄáäáíáÉë=íç=éêçÇìÅÉ=ä~êÖÉ=~ãçìåíë=
çÑ=Äáçã~ëë=~í=îÉêó=äçï=ÅçëíK=eçïÉîÉêI=~ë=ãÉåíáçåÉÇ=éêÉîáçìëäóI=çåÉ=
çÑ= íÜÉ= åÉÖ~íáîÉ= ~ëéÉÅíë= çÑ= ìëáåÖ= bK= Åçäá= áë= íÜÉ= Ñçêã~íáçå= çÑ= áåÅäìëáçå=
ÄçÇáÉëK= qç= éêçéÉêäó= ìåÇÉêëí~åÇ= ïÜó= áåÅäìëáçå= ÄçÇáÉë= ~êÉ= ÑçêãÉÇI= ~=
ÄêáÉÑ=áåíêçÇìÅíáçå=íç=íê~åëÅêáéíáçåI=íê~åëä~íáçåI=~åÇ=ÑçäÇáåÖ=áå=bK=Åçäá=áë=
åÉÉÇÉÇK=
=
Transcription
qÜÉ= íê~åëÅêáéíáçå= çÑ= ak^= áåíç= ãok^= áë= éÉêÑçêãÉÇ= Äó= íÜÉ= ok^=
éçäóãÉê~ëÉK= qÜÉ= éçäóãÉê~ëÉ= ÄáåÇë= íç= éêçãçíÉê= êÉÖáçåë= äçÅ~íÉÇ=
=========================================
R=ÜííéWLLí~êÖÉíÇÄKéÇÄKçêÖLëí~íáëíáÅëLq~êÖÉípí~íáëíáÅëKÜíãä=
= NT
ìéëíêÉ~ã=çÑ=íÜÉ= ÖÉåÉK=qÜÉ= ÄáåÇáåÖ=çÑ=ok^=éçäóãÉê~ëÉ=íç=ak^=Å~å=
ÉáíÜÉê=ÄÉ=ëíáãìä~íÉÇ=çê=êÉéêÉëëÉÇ=Äó=ÇáÑÑÉêÉåí=éêçíÉáåëK=låÉ=çÑ=íÜÉ=Ñáêëí=
éêçãçíÉêë=íç=ÄÉ=ëíìÇáÉÇ=áå=ÇÉí~áä=ï~ë=íÜÉ=ä~Å=éêçãçíÉê=xPVI=QMzK=få=bK=
Åçäá=íÜÉ=ä~Å=éêçãçíÉê=êÉÖìä~íÉë= íÜÉ= íê~åëÅêáéíáçå=çÑ=ÖÉåÉë=áåîçäîÉÇ=áå=
íÜÉ= Å~í~Äçäáëã= çÑ= ä~ÅíçëÉI= ïÜáÅÜ= Éå~ÄäÉë= íÜÉ= Ä~ÅíÉêá~= íç= êÉëéçåÇ= íç=
ÅÜ~åÖÉë=çÑ=åìíêáÉåí=äÉîÉäë=áå=áíë=ÉåîáêçåãÉåíK==
páåÅÉ=íÜÉ=çîÉêÉñéêÉëëáçå=çÑ=ÑçêÉáÖå=éêçíÉáåë=áå=bK=Åçäá=áë=~=Ñ~áêäó=Ü~êÇ=
ãÉí~ÄçäáÅ=ÄìêÇÉå=Ñçê=bK=ÅçäáI=áí=áë=ÇÉëáê~ÄäÉ=íç=Ü~îÉ=~=íáÖÜíäó=~åÇ=ÜáÖÜäó=
Åçåíêçää~ÄäÉ=éêçãçíÉêK=
aÉí~áäÉÇ= âåçïäÉÇÖÉ= çÑ= íÜÉ= ä~Å= éêçãçíÉê= ã~ÇÉ= áí= çåÉ= çÑ= íÜÉ= Ñáêëí=
éêçãçíÉêë=íç=ÄÉ=áåÅçêéçê~íÉÇ=áåíç=ÉñéêÉëëáçå=îÉÅíçêëK=qçÇ~ó=íÜÉêÉ=~êÉ=
~=ãìäíáíìÇÉ=çÑ=ÇáÑÑÉêÉåí=éêçãçíÉêë=ìëÉÇ=áå=ÉñéêÉëëáçå=îÉÅíçêëK=^ãçåÖ=
íÜÉ=ãçëí=Åçããçå=çåÉë=~êÉ=íÜÉ=ä~Å=éêçãçíÉêI=íÜÉ=~ê~ÄáåçëÉ=éêçãçíÉê=
xQNzI= ~= éêçãçíÉê= Ñêçã= íÜÉ= qR= éÜ~ÖÉ= xQOzI= ~åÇ= éêçÄ~Ääó= íÜÉ= ãçëí=
ïáÇÉäó= ìëÉÇ= íçÇ~óI= íÜÉ= qT= éêçãçíÉê= xOMzK= qÜÉ= Ñáêëí= íÜêÉÉ= éêçãçíÉêë=
ìíáäáòÉ= ÉåÇçÖÉåçìë= bK= Åçäá= ok^= éçäóãÉê~ëÉI= ïÜáäÉ= íÜÉ= qT= éêçãçíÉê=
êÉèìáêÉë= qT= ok^= éçäóãÉê~ëÉK= qÜÉ= qT= ok^= éçäóãÉê~ëÉ= áë= ÉáíÜÉê=
éêçîáÇÉÇ= çå= ~å= Éñíê~= éä~ëãáÇ= çê= áåÅçêéçê~íÉÇ= áå= íÜÉ= ÖÉåçãÉ= çÑ= íÜÉ=
Üçëí=ëíê~áåK=qÜÉ=ÉñéêÉëëáçå=çÑ=íÜÉ=qT=éçäóãÉê~ëÉ=áë=ìëì~ääó=ìåÇÉê=íÜÉ=
Åçåíêçä=çÑ=íÜÉ=ä~Å=éêçãçíÉêK=qÜÉ=qT=éçäóãÉê~ëÉ=áë=~å=Éñíê~çêÇáå~êáäó=
ÉÑÑáÅáÉåí=ok^=éçäóãÉê~ëÉ=~åÇ=ÉñíêÉãÉäó=ÜáÖÜ=äÉîÉäë=çÑ=íÜÉ=ãok^=çÑ=
áåíÉêÉëí= Å~å= ÄÉ= çÄí~áåÉÇ= íÜ~í= åÉ~êäó= ë~íìê~íÉ= íÜÉ= íê~åëä~íáçå~ä=
ã~ÅÜáåÉêó=çÑ=íÜÉ=ÅÉää=xOMzK=
=
Translation
få= bK= ÅçäáI= ÄáåÇáåÖ= çÑ= íÜÉ= êáÄçëçãÉë= íç= íÜÉ= ãok^= çÅÅìêë= ïÜáäÉ= íÜÉ=
ãok^=áë=ÄÉáåÖ=ëóåíÜÉëáòÉÇK==qÜáë=éêçÅÉëë=áë=áåáíá~íÉÇ=Äó=íÜÉ=ÄáåÇáåÖ=çÑ=
íÜÉ=PMp=ëìÄìåáí=íç=~=ëéÉÅáÑáÅ=ëÉèìÉåÅÉ=áå=íÜÉ=ok^I=íÜÉ=pÜáåÉJaÉäÖ~êåç=
EpaF= ëÉèìÉåÅÉ= çê= êáÄçëçãÉ= ÄáåÇáåÖ= ëáíÉ= Eo_pFK= qÜÉ= pa= ëÉèìÉåÅÉ= áë=
äçÅ~íÉÇ= UJNP= åìÅäÉçíáÇÉë= RÛ= çÑ= íÜÉ= ëí~êí= ÅçÇçå= E^rdFK= qÜÉ= pa=
áåíÉê~Åíáçå=ÖìáÇÉë=íÜÉ=êáÄçëçãÉ=íÜÉ=êáÖÜí=éçëáíáçå=êÉä~íáîÉ=íç=íÜÉ=ëí~êí=
ÅçÇçåK= qÜÉ= åÉñí= ëíÉé= áå= íÜÉ= íê~åëä~íáçå~ä= áåáíá~íáçå= éêçÅÉëë= áë= íÜÉ=
ÄáåÇáåÖ=çÑ=ëéÉÅá~ä=íok^=EÑjÉíJíok^F=íç=íÜÉ=^rd=ëí~êí=ÅçÇçå=áå=íÜÉ=
ãok^K= qÜáë= áë= ÑçääçïÉÇ= Äó= íÜÉ= ÄáåÇáåÖ= çÑ= íÜÉ= RMp= ëìÄìåáí= çÑ= íÜÉ=
= NU
êáÄçëçãÉI=êÉëìäíáåÖ=áå=~=ÑìåÅíáçå~ä=TMp=êáÄçëçãÉ=Å~ääÉÇ=íÜÉ=áåáíá~íáçå=
ÅçãéäÉñK=qÜÉ=åÉñí=ëíÉé=áå=íÜÉ=íê~åëä~íáçå=éêçÅÉëë=áë=ÉäçåÖ~íáçåK=qÜáë=áë=
~ÅÜáÉîÉÇ=Äó=íÜÉ=ëÉèìÉåíá~ä=~ÇÇáíáçå=çÑ=íok^=ãçäÉÅìäÉë=äç~ÇÉÇ=ïáíÜ=~å=
~ãáåç=~ÅáÇ=E^ãáåç~ÅóäJíok^F=íç=íÜÉ=êáÄçëçãÉK=qÜÉ=íÜêÉÉ=Ä~ëÉë=íÜ~í=
ã~âÉ=ìé=çåÉ=ÅçÇçå=áå=íÜÉ=ãok^=~êÉ=êÉÅçÖåáòÉÇ=Äó=~=ëéÉÅá~ä=ëíêìÅíìêÉ=
áå=íÜÉ=íok^I=íÜÉ=~åíáÅçÇçå=~êãK=få=íÜáë=ã~ååÉêI=~ãáåç=~ÅáÇ=Äó=~ãáåç=
~ÅáÇ= áë=~ÇÇÉÇ=íç=íÜÉ=ÖêçïáåÖ=éçäóéÉéíáÇÉ=ÅÜ~áåK= qÜÉ=åÉñí=ëíÉé= áë= íÜÉ=
íÉêãáå~íáçå=çÑ=íÜÉ=éçäóéÉéíáÇÉ=ëóåíÜÉëáëK=få=íÜÉ=ãok^=íÜÉêÉ=~êÉ=íÜêÉÉ=
ÅçÇçåë= íÜ~í= Çç= åçí= ÅçÇÉ= Ñçê= ~ãáåç= ~ÅáÇëI= Äìí= áåëíÉ~Ç= ëáÖå~ä= íÜÉ=
íÉêãáå~íáçå= çÑ= íê~åëä~íáçåK= péÉÅá~ä= íÉêãáå~íáçå= Ñ~Åíçêë= êÉÅçÖåáòÉ= íÜáë=
ëÉèìÉåÅÉ=~åÇ=íÜÉ=íê~åëä~íáçå=áë=íÉêãáå~íÉÇK==
=
Folding
qÜÉ=äáåÉ~ê=éçäóéÉéíáÇÉ=íÜ~í=Ü~ë=ÄÉÉå=ëóåíÜÉëáòÉÇ=Äó=íÜÉ=êáÄçëçãÉ=Ü~ë=
íç= ÑçäÇ= áåíç= áíë= å~íáîÉ= íÜêÉÉ= ÇáãÉåëáçå~ä= ëíêìÅíìêÉK= ^ää= çÑ= íÜÉ=
áåÑçêã~íáçå=åÉÉÇÉÇ=íç=ÑçäÇ=~=äáåÉ~ê=éçäóéÉéíáÇÉ=áåíç=íÜÉ=ÅçêêÉÅí=íÜêÉÉ=
ÇáãÉåëáçå~ä= ëíêìÅíìêÉ= áë= éêÉëÉåí= áå= íÜÉ= ~ãáåç= ~ÅáÇ= ëÉèìÉåÅÉK= qÜáë= áë=
áääìëíê~íÉÇ= Äó= íÜÉ= Ñ~Åí= íÜ~í= ÅçãéäÉíÉäó= ìåÑçäÇÉÇ= éÉéíáÇÉë= Å~å= êÉ~ÅÜ=
íÜÉáê=å~íáîÉ=ÅçåÑçêã~íáçå=áå=îáíêç=xQPzK=fí=áë=~äëç=ïçêíÜ=åçíáåÖ=íÜ~í=íÜÉ=
å~íáîÉ= ÅçåÑçêã~íáçå= çÑ= ~= éêçíÉáå= áë= ~äãçëí= ÉñÅäìëáîÉäó= íÜÉ=
ÅçåÑçêã~íáçå= ïáíÜ= íÜÉ= äçïÉëí= ÑêÉÉ= ÉåÉêÖó= xQQzK= eçïÉîÉê= íÜÉ= ÉåÉêÖó=
ÇáÑÑÉêÉåÅÉ= ÄÉíïÉÉå= íÜÉ= ÑçäÇÉÇ= ~åÇ= ìåÑçäÇÉÇ= ëí~íÉë= áë= ÖÉåÉê~ääó= îÉêó=
ëã~ääK=
qÜÉ=ÇÉí~áäë=çÑ=éêçíÉáå=ÑçäÇáåÖ=~êÉ=åçí=óÉí=ÅçãéäÉíÉäó=ìåÇÉêëíççÇI=Äìí=
áå= íÜÉ= ä~ëí= ÇÉÅ~ÇÉ= ëáÖåáÑáÅ~åí= éêçÖêÉëë= Ü~ë= ÄÉÉå= ã~ÇÉK= qÜÉ= ÅÉåíê~ä=
éêçÄäÉã=ïáíÜ=éêçíÉáå=ÑçäÇáåÖ=áë=ìåÇÉêëí~åÇáåÖ=Üçï=~=éêçíÉáå=êÉ~ÅÜÉë=
áíë=å~íáîÉ=íÜêÉÉ=ÇáãÉåëáçå~ä=ëíêìÅíìêÉ=ïÜÉå=íÜÉêÉ=~êÉ=~äãçëí=~å=áåÑáåáíÉ=
åìãÄÉê=çÑ=éçëëáÄäÉ=ëíêìÅíìê~ä=ÅçåÑçêã~íáçåëK=fÑ=ÉîÉêó=~ãáåç=~ÅáÇ=Å~å=
~Ççéí= íïç= ÇáÑÑÉêÉåí= ã~áå= ÅÜ~áå= ÅçåÑçêã~íáçåëI= íÜÉå= íÜÉêÉ= ~êÉ= ãçêÉ=
íÜ~å=úNMPM=éçëëáÄäÉ=ÅçåÑçêã~íáçåë=Ñçê=~=NMM=~~=äçåÖ=éçäóéÉéíáÇÉK=bîÉå=
áÑ= íÜÉëÉ= ÅçåÑçêã~íáçåë= ïÉêÉ= ë~ãéäÉÇ= ~ë= Ñ~ëí= ~ë= íÜÉ= ä~ïë= çÑ= éÜóëáÅë=
ïçìäÇ= ~ääçïI= áí= ïçìäÇ= í~âÉ= ãçêÉ= íÜ~å= NMNN=óÉ~êë= íç= ë~ãéäÉ= ~ää= íÜÉëÉ=
ÅçåÑçêã~íáçåë= xQQzK= qÜÉ= ÑçäÇáåÖ= çÑ= éêçíÉáåë= Å~å= íÜÉêÉÑçêÉ= åçí= ÄÉ= ~=
ÅçãéäÉíÉäó=ê~åÇçã=éêçÅÉëëK==
= NV
qÜÉ= ÅìêêÉåí= ëÅáÉåíáÑáÅ= îáÉï= çÑ= éêçíÉáå= ÑçäÇáåÖ= áë= Ä~ëÉÇ= çå= ÉåÉêÖó=
ëìêÑ~ÅÉë=çê=ÑìååÉäë=xQQI=QRzK=qÜÉ=éçäóéÉéíáÇÉ=ëí~êíë=~í=íÜÉ=íçé=çÑ=íÜÉ=
ÉåÉêÖó=ä~åÇëÅ~éÉ=~ë=~=ê~åÇçã=Åçáä=Äìí=Åçää~éëÉë=íç=~=íê~åëáíáçå=ëí~íÉ=çê=
~å=áåíÉêãÉÇá~íÉ=ÑìêíÜÉê=Ççïå=íÜÉ=ä~åÇëÅ~éÉK=qÜÉ=ÇêáîáåÖ=ÑçêÅÉ=ÄÉÜáåÇ=
íÜáë=Åçää~éëÉ=áë=íÜÉ=ÅçåÇÉåë~íáçå=çÑ=ÜóÇêçéÜçÄáÅ=~ãáåç=~ÅáÇë=íç=êÉÇìÅÉ=
íÜÉáê= ÉñéçëìêÉ= íç= íÜÉ= ÜóÇêçéÜáäáÅ= ëçäîÉåíI= íÜÉ= ÜóÇêçéÜçÄáÅ= ÉÑÑÉÅíK= få=
íÜáë=íê~åëáíáçå=ëí~íÉ=ëÉîÉê~ä=ëí~ÄäÉ=“å~íáîÉ=äáâÉÒ=Åçåí~Åíë=ÑçêãK==
qÜÉëÉ=Åçåí~Åíë=~êÉ=ãçêÉ=ëí~ÄäÉ=íÜ~å=åçåJå~íáîÉ=ÅçåÑçêã~íáçåë=~åÇ=~êÉ=
íÜÉêÉÑçêÉ=ãçêÉ=äçåÖJäáîÉÇK=cêçã=íÜáë=ÑçäÇáåÖ=áåíÉêãÉÇá~íÉ=íÜÉ=éêçíÉáå=
íÜÉå= êÉ~ÅÜÉë= áíë= å~íáîÉ= ÅçåÑçêã~íáçå= ~í= íÜÉ= Äçííçã= çÑ= íÜÉ= ÉåÉêÖó=
ä~åÇëÅ~éÉK= fÑ= íÜÉ= ÉåÉêÖó= ä~åÇëÅ~éÉ= Ü~ë= íÜÉ= êáÖÜí= “ëÜ~éÉÒI= çåäó= ~=
äáãáíÉÇ=åìãÄÉê=çÑ=~ää=éçëëáÄäÉ=ÅçåÑçêã~íáçåë=~êÉ=ë~ãéäÉÇ=~åÇ=áí=áë=íÜáë=
“ëÜ~éÉÒ= çÑ= íÜÉ= ÉåÉêÖó= ä~åÇëÅ~éÉ= íÜ~í= áë= ÉåÅçÇÉÇ= áå= íÜÉ= ~ãáåç= ~ÅáÇë=
ëÉèìÉåÅÉ=xQSzK==
Soluble Proteins
fí=Ü~ë=ÄÉÉå=Éëíáã~íÉÇ=íÜ~í=íÜÉ=ÅçåÅÉåíê~íáçå=çÑ=ã~ÅêçãçäÉÅìäÉë=áå=íÜÉ=
Åóíçéä~ëã= áë= ÄÉíïÉÉå= PMMJQMM= ãÖLãäI= ïÜáÅÜ= ã~âÉë= áí= îÉêó= ÅêçïÇÉÇ=
~åÇ= ~äãçëí= ÖÉäJäáâÉ= xQTzK= qÜÉ= ÑçäÇáåÖ= çÑ= íÜÉ= äáåÉ~ê= éçäóéÉéíáÇÉ= ÅÜ~áå=
áåíç=íÜÉ=ÅçêêÉÅí=íÜêÉÉ=ÇáãÉåëáçå~ä=ëíêìÅíìêÉ=áë=åçí=~=íêáîá~ä=í~ëâ=áå=íÜÉ=
ÅêçïÇÉÇ= Åóíçéä~ëã= çÑ= íÜÉ= bK= Åçäá= ÅÉääK= få= ÖÉåÉê~ä= ëã~ääI= çåÉ= Ççã~áå=
éêçíÉáåë= ÑçäÇ= ê~éáÇäó= áå= bK= Åçäá= xQUzI= ÜçïÉîÉêI= ä~êÖÉê= ãìäíáJÇçã~áå=
éêçíÉáåë= ãáÖÜí= êÉèìáêÉ= íÜÉ= ÜÉäé= çÑ= ÑçäÇáåÖ= ãçÇìä~íçêëI= ïÜáÅÜ= ~êÉ=
âåçïå= ~ë=ÅÜ~éÉêçåÉëK= qÜÉêÉ=~êÉ=áå=éêáåÅáé~ä= íÜêÉÉ=ÇáÑÑÉêÉåí=âáåÇë=çÑ=
ÅÜ~éÉêçåÉë= áå= bK= ÅçäáW= ÑçäÇáåÖ= ÅÜ~éÉêçåÉëI= ÜçäÇáåÖ= ÅÜ~éÉêçåÉë= ~åÇ=
Çáë~ÖÖêÉÖ~íáåÖ=ÅÜ~éÉêçåÉëK==
=
Folding Chaperones
^ë=íÜÉ=å~ëÅÉåí=éçäóéÉéíáÇÉ=ÅÜ~áå=Éñáíë=íÜÉ=êáÄçëçãÉ=áí=Å~å=ÉáíÜÉê=ÑçäÇ=
ëéçåí~åÉçìëäó=áåíç=áíë=å~íáîÉ=ÅçåÑçêã~íáçå=çê=ÄÉ=~=í~êÖÉí=Ñçê=ÑçäÇáåÖ=
ÅÜ~éÉêçåÉë= EcáÖìêÉ= PFK= qÜÉëÉ= ÑçäÇáåÖ= ÅÜ~éÉêçåÉë= Ü~îÉ= íÜÉ= êçäÉ= çÑ=
ëÜáÉäÇáåÖ=ÜóÇêçéÜçÄáÅ=ëíêÉíÅÜÉë=áå=íÜÉ=å~íáîÉ=éçäóéÉéíáÇÉ=ÅÜ~áåI=ïÜáÅÜ=
~êÉ= îÉêó= éêçåÉ= íç= ~ÖÖêÉÖ~íáçåK= qÜÉêÉ= ~êÉ= íÜêÉÉ= ÇáÑÑÉêÉåí= ÑçäÇáåÖ=
ÅÜ~éÉêçåÉ= Åä~ëëÉë= áå= bK= ÅçäáI= íÜÉ= íêáÖÖÉê= Ñ~Åíçê= EqcFI= aå~hLaå~g= ~åÇ=
= OM
dêçbiK= =qÜÉ=íêáÖÖÉê= Ñ~ÅíçêI=ïÜáÅÜ=áë=ÄçìåÇ=íç=íÜÉ=êáÄçëçãÉ=áå=ÅäçëÉ=
îáÅáåáíó= íç= íÜÉ= Éñáí= íìååÉäI= Ü~ë= í~êÖÉíë= ïÜáÅÜ= ~êÉ= íóéáÅ~ääó= ä~êÖÉ= E[SM=
âa~F=ãìäíáJÇçã~áå=éêçíÉáåë=xQUzK=qÜÉ=ÑìåÅíáçå=çÑ=qc=áë=íÜçìÖÜí=íç=ÄÉ=
“ëÅ~ååáåÖÒ= íÜÉ= å~ëÅÉåí= éçäóéÉéíáÇÉ= ÅÜ~áå= Ñçê= ÜóÇêçéÜçÄáÅ= ëíêÉíÅÜÉë=
~åÇ=ëÜáÉäÇáåÖ=íÜÉã=xQVzK=aå~h=Ü~ë=~=ëáãáä~ê=ëìÄëíê~íÉ=ëéÉÅáÑáÅáíó=~ë=qc=
Äìí=áë=ÖìáÇÉÇ=íç=íÜÉ=ÜóÇêçéÜçÄáÅ=ëíêÉíÅÜÉë=Äó=íÜÉ=ÅçJÅÜ~éÉêçåÉ=aå~gK=
qÜÉ= ÄáåÇáåÖ= çÑ= aå~h= íç= íÜÉ= éçäóéÉéíáÇÉ= ÅÜ~áå= áë= ÅçìéäÉÇ= ïáíÜ= ^qm=
ÜóÇêçäóëáë= Äó= aå~hK= qÜÉ= ëìÄëíê~íÉ= áë= êÉäÉ~ëÉÇ= Ñêçã= aå~h= Äó= íÜÉ=
ÉñÅÜ~åÖÉ=çÑ=^am=íç=^qmI=ÅçåíêçääÉÇ=Äó=íÜÉ=dêéb=éêçíÉáåK=tÜÉå=íÜÉ=
éêçíÉáå=áë=êÉäÉ~ëÉÇI=áí=ãáÖÜí=êÉ~ÅÜ=áíë=å~íáîÉ=ÅçåÑçêã~íáçå=çê=ìåÇÉêÖç=~=
ëÉêáÉë=çÑ=aå~h=ÅóÅäÉëK=qÜÉ=éçäóéÉéíáÇÉ=ÅÜ~áå=ãáÖÜí=~äëç=ÄÉ=í~êÖÉíÉÇ=íç=
íÜÉ= dêçbiJdêçbp= ÅÜ~éÉêçåáå= ëóëíÉãK= dêçbi= áë= ~= îÉêó= ä~êÖÉ= EúUMM=
âa~F=éêçíÉáå=ÅçãéäÉñ=ÅçåëáëíáåÖ=çÑ=íïç=ëí~ÅâÉÇ=ÜÉéí~ãÉêáÅ=êáåÖëK=få=
áíë= çéÉå= ÑçêãI= íÜÉ= ÅÉåíê~ä= Å~îáíó= çÑ= dêçbi= áë= äáåÉÇ= ïáíÜ= ÉñéçëÉÇ=
ÜóÇêçéÜçÄáÅ= ~ãáåç= ~ÅáÇëI= Ñ~Åáäáí~íáåÖ= íÜÉ= ÄáåÇáåÖ= íç= é~êíäó= ÑçäÇÉÇ=
éçäóéÉéíáÇÉëK= réçå= ÄáåÇáåÖ= çÑ= dêçbp= íç= dêçbiI= ^qm= ÜóÇêçäóëáë=
çÅÅìêë= ~åÇ= íÜÉ= ÅçãéäÉñ= ìåÇÉêÖçÉë= ~= ä~êÖÉ= ÅçåÑçêã~íáçå~ä= ÅÜ~åÖÉ=
ïÜáÅÜ=äÉ~Çë=íç=íÜÉ=“êÉãçî~äÒ=çÑ=íÜÉ=ÜóÇêçéÜçÄáÅ=~ãáåç=~ÅáÇë=äáåáåÖ=
íÜÉ=Å~îáíó=ï~ääK=fí=áë=áå=íÜáë=éêçÅÉëë=íÜ~í=íÜÉ=éêçíÉáå=áåëáÇÉ=íÜÉ=dêçbiJ dêçbp= ÅçãéäÉñ= ÑçäÇë= xRMzK= eçïÉîÉêI= ãçëí= çÑ= íÜÉ= éêçíÉáåë= êÉäÉ~ëÉÇ=
Ñêçã= dêçbiJdêçbp= ~êÉ= åçí= áå= íÜÉ= å~íáîÉ= ëí~íÉ= ~åÇ= ~êÉ= íÜÉêÉÑçêÉ=
ëìÄàÉÅíÉÇ=íç=~åçíÜÉê=êçìåÇ=çÑ=ÑçäÇáåÖ=áå=íÜÉ=ÅÜ~éÉêçåáåK==
=
Holding Chaperones
réçå= ÉåîáêçåãÉåí~ä= ëíêÉëëI= ëìÅÜ= ~ë= íÉãéÉê~íìêÉ= çê= çñáÇ~íáîÉ= ëíêÉëëI=
ÜçäÇáåÖ=ÅÜ~éÉêçåÉë=ÄáåÇ=íç=é~êíäó= ìåÑçäÇÉÇ= éêçíÉáåëI=ïÜáÅÜ=éêÉîÉåíë=
íÜÉ= ìåÑçäÇÉÇ= éêçíÉáåë= Ñêçã= ~ÖÖêÉÖ~íáåÖ= xQUz= EcáÖìêÉ= PFK= qÜÉ= ÜçäÇáåÖ=
ÅÜ~éÉêçåÉë= Çç= åçí= ~ÅíáîÉäó= ~ëëáëí= áå= íÜÉ= ÑçäÇáåÖ= çÑ= íÜÉ= éêçíÉáåI= Äìí=
áåëíÉ~Ç=é~ëë=íÜÉ=éêçíÉáå=íç=íÜÉ= aå~hLaå~g= çê= dêçbiJdêçbp=ëóëíÉãë=
ïÜÉå=íÜÉ=ëíêÉëë=Ü~ë=ÄÉÉå=êÉäáÉîÉÇK=eçïÉîÉêI=áÑ=íÜÉ=ëíêÉëë=ÅçåÇáíáçå=áë=
éêçäçåÖÉÇI=íÜÉ=ÅÜ~éÉêçåÉ=ëóëíÉãë=~êÉ=ë~íìê~íÉÇ=~åÇ=íÜÉ=Ñçêã~íáçå=çÑ=
áåÅäìëáçå=ÄçÇáÉë=áë=áåÉîáí~ÄäÉK=
=