高等教学大一英语下课件：Protein-Structure-and-Function

1ChapterIII

ProteinStructureandFunction1ChapterIII

ProteinStructure2(I)Secondary

Structure：

Thelocalspatialarrangementofaminoacidresiduesthatarenearbyinthesequence,thatis,therelativepositionsofbackboneatomsofacertainpeptidesegment.Thesidechainsarenotconsidered.

Forms:α

helix,β

pleatedsheet,β

turn,π

helix,

randomcoilMajorBond：Hydrogenbond

I.ConformationofProtein2(I)SecondaryStructure：I.C3Right-handedhelix3.6aminoacidresiduesperturnofhelixThepitchofthehelixis0.54nm,diameteris0.23nmTheN-Hofeverypeptidebondishydrogen-bondedtotheC=Oofneighboringpeptidebondlocatedfourpeptidebondsawayinthesamechain.,including13atoms

,soalsoknownas3.613helix.AllthemainchainC=OandNHarehydrogenbonded.LinusPauling

1.α-helix(1)3Right-handedhelixLinusPauli44Thealphahelixisacoiledsecondarystructureduetoahydrogenbondeveryfourthaminoacid5Thealphahelixisacoiledse6Directionofhydrogenbondsareparalleltotheverticalaxisofhelix.Thestabilityofanα-helixarisesprimarilyfromhydrogenbonds.Thesidechainsareontheoutsideofthehelix,notdirectlyparticipateintheformationofhelix.α-helixisthemoststablesecondaryconformation1.

-helix(2)：6Directionofhydrogenbondsa778Adjacentpeptideunitformazigzagorpleatedpattern,

theintersectionangleis110。.β-Sheetsarestabilizedbyhydrogenbondingbetweenpolypeptidestrands.

Thedirectionofhydrogenbondsareverticaltothepeptidestrands.

Adjacentchainsinabsheetcanruninoppositedirections(antiparallelbsheet)orinthesamedirection(parallelbsheet).Thesidechainsofadjacentaminoacidspointinoppositedirections2.β-pleatedsheetstructure8Adjacentpeptideunitforma99101011Peptidechainarisesatight180°turn.

Aβ-turninvolvesfouraminoacidresidues,thefirstresiduesishydrogenbondedtothefourth.Prolineisoftenpresentinβ-turnOftenlieontheglobulinsurfaceandservekeybiologicrole.

3.β-turn11Peptidechainarisesatight121213Left-handedhelix，4.4aminoacidresiduesperturn.Hydrogenbondsstabilizetheπ-helix，everyhydrogenbondacross18atoms,soalsonamedas4.418

helix.Oftenfoundincollagen.Tripleleft-handedhelixestwisttoformright-handedsuperhelixandturntocollagenousfibers.4.π-helix13Left-handedhelix，4.4amino141415Generalnameofaseriesofunorderedconformationinprotein.

Importantstructuralandfunctionalsegmentsofprotein.5.RandomCoil15Generalnameofaseriesof16Somesecondarystructureunitsarecloseenoughinspacetoformregularsupersecondarystructureunits,suchasααα，βββ，βαβ，alsonamedasmotif（模体).Intermediatelevelbetweensecondaryandtertiarystructures6.Supersecondary

StructureααofCytochromeCΒαβofPCNAΒβofplasminogen16Somesecondarystructureuni17MotifinCalcium-bindingProteinZincFinger

17MotifinCalcium-bindingProSidechainscandisruptorinducetheformationofsecondarystructure

Shape:Prohavingarigidring(

–helixdisrupter)Size:

–helixand

-sheetneedsAAsofsmallsidechain.Leu,Ile,Trp,andAsn,havingbulkysides,hardtoformα–helixandβ-sheet)Charge:ToomanychargedAAsinashortregionofonepeptideishardtoform

–helix.18Sidechainscandisruptorind19*Definition:Theentirethree-dimensionalconformationofapolypeptidechain.Itreferstothespatialarrangementofaminoacidresiduesthatarefarapartinthesequenceandtothepatternofdisulfidebonds.Itindicates,inthree-dimensionalspace,howsecondarystructuralassembletoformdomainsandhowthesedomainsrelatespatiallytooneanother.(II)Tertiary

Structure19*Definition:(II)TertiarySt20Singleorseveralsupersecondarystructureunitsgatherandfoldindependentlyintoacompact,stablestructure,termeddomain.Domainisthefunctionelementofprotein.Thedifferentdomainsofaproteinareoftenassociatedwithdifferentfunctions.Domainisthepartialfoldingregionattheleveloftertiarystructure.

Motifisitssubunit.Everydomainisencodedbyoneexon.Domain（结构域）20Singleorseveralsuperseco21NADHPyruvateLactateDehydrogenaseNterminalCterminal21NADHPyruvateLactateDehydrog

EGFReceptorIntracellularproteinkinasedomainisregulatedviathebindingofthepeptidehormoneEGFtoitsextracellulardomain.22EGFReceptorIntracellularpro23*Features：

Tothesinglepeptideprotein,tertiarystructureisthehighestlevelofstructure.

Formhydrophilicsurfaceandhydrophobicinnercore.*MajorBond：HydrophobicInteraction23*Features：24Myoglobin(肌红蛋白)24Myoglobin(肌红蛋白)25Quaternarystructuredefinesthepolypeptidecompositionofaproteinforanoligomericprotein,andthespatialrelationshipsbetweenitssubunits.Subunit（亚基）

Eachpolypeptidechaininsuchaproteiniscalledasubunit.

Subunitisinactivewhenitexistsalone.(III)

Quaternary

Structure25Quaternarystructuredefines26Features:QuarternarystructureariseswhentwoormorepolypeptidesjointoformaproteinSubunitisinactivewhenitexistsonitsown.Subunitsarelinkedbysecondarybonds（H-bonds,ionicinteractions,andhydrophobicinteractions）Ifthepeptidechainsarelinkedbycovalentbonds(disulfidebond)，itisnotbelongtoquaternarystructure.Polypeptidechainscanbeindimer,trimer..,aswellashomo-orhetero-form.26Features:Forexample,hemoglobiniscomposedof4polypeptidechainsLinktovideo27Forexample,hemoglobiniscomNH3＋

COO－

β2

NH3＋

COO－

α2

COO－NH3＋

β1COO－NH3＋

α1AspHisArgAspLysLysAspArgHisAsp94146141126404012614114694IonicForcesinHemoglobinQuaternaryStructureofHemoglobin28NH3＋292930

PrimaryStructure：Peptidebond、Disulfidebond

SecondaryStructure：Hydrogenbond

TertiaryStructure：Hydrophobicinteraction

QuaternaryStructure：Ionicbond

(IV)Non-covalentBondsstabilizeProteinStructure30PrimaryStructure：Peptide3131HydrogenbondAhydrogenatomissharedbytwootheratoms.H-donor:theatomtowhichHatomismoretightlyattached,andtheotherisH-acceptor.32HydrogenbondAhydrogenatomiHydrophobicinteractionNonpolarmoleculestendtoclustertogetherinwater,thatis,aminoacidswithnonpolarsidechainsclusterinthecoreoftheprotein,outofcontactwithwater33HydrophobicinteractionNonpolaAchargedgroupisabletoattractanothergroupofoppositecharges.Ionicinteraction34AchargedgroupisabletoattTheattractionbetweenapairofatomsincreasesastheycomecloser,untiltheyarerepelledbyvanderWaalscontactdistance.vanderWaalsforce

35TheattractionbetweenapairDisulfidebridgeStrongcovalentbondsbetweensulfuratomsintheaminoacidcysteine36DisulfidebridgeStrongcovaleThefoldingofmanyproteinsisprotectedbychaperoninproteinsthatshieldoutbadinfluences.

Chaperon37ThefoldingofmanyproteinsiPost-translationalModification38Post-translationalModificatio39II.Structure-FunctionRelationshipofProteinsSequenceofDNA

AminoacidsequenceofproteinConformationofProteinFunctionofProteinPrimarystructureisbasis,Conformationisthekeyfactor.39II.Structure-FunctionRelat401.ThealternationofkeyAAsinaproteinwillcausethelossofitsbiologicalfunctions

Sicklecellanemia

Abnormalhemoglobin,

developbecauseofasingleaminoacidsubstitution.Thisisthefirstcaseofmoleculardiseaseidentifiedinhistory(I)PrimaryStructureandFunction401.ThealternationofkeyAAs41Oxygen-carryingcapacityofHbSdrop.

Theabnormalredcellsarethin,elongated,sickle-shaped.Sicklingdecreasesthecellsflexibilityandcauseshemolysis.HbAβ

Val-His-Leu-Thr-Pro-Glu-Glu-Lys…HbSβ

Val-His-Leu-Thr-Pro-Val-Glu-Lys…41Oxygen-carryingcapacityof424243

分子病相应蛋白质分子的异常或缺失镰状细胞贫血血红蛋白家族性高胆固醇血症低密度脂蛋白受体原发性痛风病磷酸核糖焦磷酸酶白化病酪氨酸酶血友病A与B凝血因子Ⅷ与Ⅸ重度联合免疫缺陷症(SCID)腺苷脱氨酶苯丙酮酸尿症苯丙氨酸羟化酶蚕豆病6-磷酸葡萄糖脱氢酶顽固性佝偻病25-羟维生素D31-羟化酶Lesch-Nyhan(自毁脸容)次黄嘌呤-鸟嘌呤磷酸综合征核糖转移酶MolecularDisease分子病Inheriteddiseasesinwhichthemanifestationsareduetoalterationsinproteinprimarystructureandfunction.TheAAvariationisduetothegenemutation.43分子病442.Proteinshavingsimilaraminoacidsequencesdemonstratethefunctionalsimilarity.

*Insulin442.Proteinshavingsimilara45ACTH

(促肾上腺皮质激素)andMSH

(促黑激素)haveasamepeptidesegment,soACTHalsohasthefunctionofpromotingmelanogenesis.45ACTH(促肾上腺皮质激素)andMSH(促黑激素46CytochromeCisaproteinwhichcanbefoundinallaerobicorganisms.

Comparisonoftheirprimarystructurecanhelptounderstandtheevolutionaryrelationshipbetweendifferentspecies.OrganismswhicharecloserintheprocessofspeciesevolutionwillhavemoresimilarprimarystructureofcytochromeC.46CytochromeCisaproteinwh47(II)SpatialstructureandfunctionProteinswillexperiencemultipleprocessestobecomecorrectlyfolded,thatis,havingacorrectstructure.Theincorrectproteinstructuremayleadtofunctionalternationordiseases.Aparticularspatialstructureofaproteinisstronglycorrelatedwithitsspecificbiologicalfunctions.47(II)Spatialstructureandf481.Amphipathicαhelix481.Amphipathicαhelix492IonChannelHydrophobicaminoacidHydrophobicaminoacidHydrophilicaminoacidCellMembrane492IonHydrophobicHydrophobic2.Thestructuralpropertiesofsilkareduetobetapleatedsheets.Thepresenceofsomanyhydrogenbondsmakeseachsilkfiberstrongerthansteel.502.Thestructuralpropertiesof51Aneffectthatariseswhenthebindingofaneffectormoleculeatthepolymericprotein'sallostericsiteregulatesproteinactivityasaresultofconformationalchanges.1)Onlyproteinswhichhavequaternarystructurepossessthisproperty.2)Allostericagentsaresmallphysiologicalmolecules,suchasO2、ATP3)Allostericsiteisasiteotherthantheprotein'sactivesite.4)Slightlychangeconformationcanincreaseordecreaseproteinactivitysubsequently.

3.Allosteric

effect（变构效应)51Aneffectthatariseswhent525253Theironatommovesintotheplaneofthehemeonoxygenation.HistidineF8anditsassociatedresiduesarepulledalongwiththeironatom.53Theironatommovesintothe54TheAllostericEffectofHemoglobins54TheAllostericEffectofHem55SchematicDiagramofAllostericEffectofHemoglobin55SchematicDiagramofAlloste5656573.蛋白质构象改变可导致构象病ProteinConformationalDisorders：Aclassofdiseasesinwhichcertainproteinsfailtofoldintotheirnormalconformationandlosetheirnormalfunction,therebydisruptthefunctionofcells,tissuesandorgansofthebody.573.蛋白质构象改变可导致构象病ProteinConfo58PathogenicMechanism：Somemisfoldingproteinsaggregateandformanti-proteaseamyloidosis,andtherebycausedisease.Diseases:Alzheimer'sdisease,Parkinson'sdisease,priondisease,type2diabetes,amyloidosis58PathogenicMechanism：Somemi59BSEisatransmissible,inheritableneurodegenerativediseasesinmammalscausedbyprionprotein

(PrP,朊病毒蛋白).NormalPrPisrichinα-helix，termedPrPc.PrPcisanormalconstituentofbraintissueinallmammals.AbnormalPrPisrichinβpleatedsheet,termedPrPsc.AnumberofPrPscaggregateextracellularlywithinthecentralnervoussystemtoformplaquesknownasamyloid,whichdestroybraintissuesbyconvertingthemtoaspongyappearancedisruptandleadtobraindamageanddeath.Bovinespongiformencephalopathy(BSE,疯牛病)59BSEisatransmissible,inhe60NH3+NH3+NH2COOHCOO-COO-PositiveIon

Zwitterion

NegativeIon（pH<PI)(pH=PI)(pH>PI)

PPPIII.

PhysicochemicalPropertiesofProtein(I)Ampholyteofprotein1.+H++H++OH－+OH―60COOHCOO-612.pIofProtein：thepHatwhichaparticularmoleculecarriesnonetelectricalcharge.3.ThechargeofproteinisrelatedtosurroundingspH.

pH<PIpositiveion

pH>PInegativeion

pH=PIelectricneutrality4.pIofmostproteinis~5.0,andnegativelychargedinbodyfluid(pH7.4)pI>7.4:basicproteins:protamine,histonepI<7.4:acidicproteins:pepsin612.pIofProtein：62SerumProteinElectrophoretogram_+

2

1

62SerumProteinElectrophoret63(II)MacromoleculeProperties1.StabilityofHydrophiliccolloidisdueto:⑴HydrationShell⑵ElectricRepulsion

2.Dialysis

3.UltracentrifugationMW:10,000～1,000,000Diameter:1~100nm,intherangeofcolloid(III)UVabsorption

max：280nm（Ty