CHAPTER5

THESTRUCTUREANDFUNCTION
OFMACROMOLECULES
SectionD:ProteinsManyStructures,ManyFunctions
1. Apolypeptideisapolymerofaminoacidsconnectedtoaspecificsequence
2. Aproteinsfunctiondependsonitsspecificconformation

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Introduction
Proteinsareinstrumentalinabouteverythingthat
anorganismdoes.
Thesefunctionsincludestructuralsupport,storage,
transportofothersubstances,intercellularsignaling,
movement,anddefenseagainstforeignsubstances.
Proteinsaretheoverwhelmingenzymesinacelland
regulatemetabolismbyselectivelyacceleratingchemical
reactions.

Humanshavetensofthousandsofdifferentproteins,
eachwiththeirownstructureandfunction.
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 Proteinsarethemoststructurallycomplex
moleculesknown.
Eachtypeofproteinhasacomplexthreedimensional
shapeorconformation.

Allproteinpolymersareconstructedfromthesame
setof20monomers,calledaminoacids.
Polymersofproteinsarecalledpolypeptides.
Aproteinconsistsofoneormorepolypeptides
foldedandcoiledintoaspecificconformation.

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1.Apolypeptideisapolymerofamino
acidsconnectedinaspecificsequence
Aminoacidsconsistoffourcomponentsattached
toacentralcarbon,thealphacarbon.
Thesecomponentsincludea
hydrogenatom,acarboxyl
group,anaminogroup,and
avariableRgroup
(orsidechain).
DifferencesinRgroups
producethe20different
aminoacids.
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 ThetwentydifferentRgroupsmaybeassimpleasa
hydrogenatom(asintheaminoacidglutamine)toa
carbonskeletonwithvariousfunctionalgroups
attached.
ThephysicalandchemicalcharacteristicsoftheR
groupdeterminetheuniquecharacteristicsofa
particularaminoacid.

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 OnegroupofaminoacidshashydrophobicR
groups.

Fig.5.15a

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 AnothergroupofaminoacidshaspolarRgroups,
makingthemhydrophilic.

Fig.5.15b

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 Thelastgroupofaminoacidsincludesthosewith
functionalgroupsthatarecharged(ionized)at
cellularpH.
SomeRgroupsarebases,othersareacids.

Fig.5.15c

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 Aminoacidsarejoinedtogetherwhena
dehydrationreactionremovesahydroxylgroup
fromthecarboxylendofoneaminoacidanda
hydrogenfromtheaminogroupofanother.
Theresultingcovalentbondiscalledapeptidebond.

Fig.5.16
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 Repeatingtheprocessoverandovercreatesalong
polypeptidechain.
Atoneendisanaminoacidwithafreeaminogroupthe
(theNterminus)andattheotherisanaminoacidwitha
freecarboxylgroupthe(theCterminus).

Therepeatedsequence(NCC)isthepolypeptide
backbone.
AttachedtothebackbonearethevariousRgroups.
Polypeptidesrangeinsizefromafewmonomersto
thousands.

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2.Aproteinsfunctiondependsonits
specificconformation
Afunctionalproteinsconsistsofoneormore
polypeptidesthathavebeenpreciselytwisted,folded,
andcoiledintoauniqueshape.
Itistheorderofaminoacidsthatdetermineswhatthe
threedimensionalconformationwillbe.

Fig.5.17
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 Aproteinsspecificconformationdeterminesits
function.
Inalmosteverycase,thefunctiondependsonits
abilitytorecognizeandbindtosomeother
molecule.
Forexample,antibodiesbindtoparticularforeign
substancesthatfittheirbindingsites.
Enzymerecognizeandbindtospecificsubstrates,
facilitatingachemicalreaction.
Neurotransmitterspasssignalsfromonecelltoanother
bybindingtoreceptorsitesonproteinsinthemembrane
ofthereceivingcell.
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 Thefoldingofaproteinfromachainofamino
acidsoccursspontaneously.
Thefunctionofaproteinisanemergentproperty
resultingfromitsspecificmolecularorder.
Threelevelsofstructure:primary,secondary,and
tertiarystructure,areusedtoorganizethefolding
withinasinglepolypeptide.
Quarternarystructureariseswhentwoormore
polypeptidesjointoformaprotein.

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 Theprimarystructureof
aproteinisitsunique
sequenceofaminoacids.
Lysozyme,anenzymethat
attacksbacteria,consists
onapolypeptidechainof
129aminoacids.
Thepreciseprimary
structureofaproteinis
determinedbyinherited
geneticinformation.

Fig.5.18
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 Evenaslightchangeinprimarystructurecanaffect
aproteinsconformationandabilitytofunction.
Inindividualswithsicklecelldisease,abnormal
hemoglobins,oxygencarryingproteins,develop
becauseofasingleaminoacidsubstitution.
Theseabnormalhemoglobinscrystallize,deformingthe
redbloodcellsandleadingtoclogsintinybloodvessels.

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Fig.5.19

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 Thesecondarystructureofaproteinresultsfrom
hydrogenbondsatregularintervalsalongthe
polypeptidebackbone.
Typicalshapes
thatdevelopfrom
secondarystructure
arecoils(analpha
helix)orfolds
(betapleated
sheets).

Fig.5.20
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 Thestructuralpropertiesofsilkareduetobeta
pleatedsheets.
Thepresenceofsomanyhydrogenbondsmakeseach
silkfiberstrongerthansteel.

Fig.5.21
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 Tertiarystructureisdeterminedbyavarietyof
interactionsamongRgroupsandbetweenRgroups
andthepolypeptidebackbone.
Theseinteractions
includehydrogen
bondsamongpolar
and/orcharged
areas,ionicbonds
betweencharged
Rgroups,and
hydrophobic
interactionsand
vanderWaals
interactionsamong
hydrophobicR
groups.

Fig.5.22

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 Whilethesethreeinteractionsarerelativelyweak,
disulfidebridges,strongcovalentbondsthatform
betweenthesulfhydrylgroups(SH)ofcysteine
monomers,stabilizethestructure.

Fig.5.22
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 Quarternarystructureresultsfromtheaggregation
oftwoormorepolypeptidesubunits.
Collagenisafibrousproteinofthreepolypeptidesthatare
supercoiledlikearope.
Thisprovidesthestructuralstrengthfortheirrolein
connectivetissue.
Hemoglobinisa
globularprotein
withtwocopies
oftwokinds
ofpolypeptides.

Fig.5.23
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Fig.5.24
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 Aproteinsconformationcanchangeinresponseto
thephysicalandchemicalconditions.
AlterationsinpH,saltconcentration,temperature,or
otherfactorscanunravelordenatureaprotein.
Theseforcesdisruptthehydrogenbonds,ionicbonds,and
disulfidebridgesthatmaintaintheproteinsshape.

Someproteinscanreturntotheirfunctionalshape
afterdenaturation,butotherscannot,especiallyin
thecrowdedenvironmentofthecell.

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Fig.5.25

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 Inspiteoftheknowledgeofthethreedimensional
shapesofover10,000proteins,itisstilldifficultto
predicttheconformationofaproteinfromits
primarystructurealone.
Mostproteinsappeartoundergoseveralintermediate
stagesbeforereachingtheirmatureconfiguration.

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 Thefoldingofmanyproteinsisprotectedby
chaperoninproteinsthatshieldoutbadinfluences.

Fig.5.26

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 Anewgenerationofsupercomputersisbeing
developedtogeneratetheconformationofany
proteinfromitsaminoacidsequenceorevenits
genesequence.
Partofthegoalistodevelopgeneralprinciplesthat
governproteinfolding.

Atpresent,scientistsuseXraycrystallographyto
determineproteinconformation.
Thistechniquerequirestheformationofacrystalofthe
proteinbeingstudied.
ThepatternofdiffractionofanXraybytheatomsofthe
crystalcanbeusedtodeterminethelocationoftheatoms
andtobuildacomputermodelofitsstructure.
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Fig.5.27
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