生物大分子结构与功能第2章相互作用力第3节第4节

第一章：蛋白质的结构层次现在是1页\一共有83页\编辑于星期三1,thesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins现在是2页\一共有83页\编辑于星期三ProteinSecondaryStructure■Secondarystructureistheregulararrangementofaminoacidresiduesinasegmentofapolypeptidechain,inwhicheachresidueisspatiallyrelatedtoitsneighborsinthesameway.■Themostcommonsecondarystructuresaretheαhelix,theβ

conformation,andβ

turns.■Thesecondarystructureofapolypeptidesegmentcanbecompletelydefinediftheφand

ψanglesareknownforallaminoacidresiduesinthatsegment.现在是3页\一共有83页\编辑于星期三10papersfromLinusPaulingandcolleaguespublishedinPNAS,1951现在是4页\一共有83页\编辑于星期三αhelix310helixπ

helix:theoreticallypossible,butneverfoundintheproteinsßsheet:parallelandanti-parallel现在是5页\一共有83页\编辑于星期三αhelixßsheet3.613helix现在是6页\一共有83页\编辑于星期三Parametersoffiveactualortheoreticalsecondarystructures:现在是7页\一共有83页\编辑于星期三αhelix:

thebackboneofthepolypeptidechainisextendedintohelicalstructureWhichIsbuiltupfromonecontinuousregion.αhelix现在是8页\一共有83页\编辑于星期三φ,ψanglepairapproximately-60°and-50°.Thelengthrangfrom4or5to44residues.Theaveragelengthisaround10residues

现在是9页\一共有83页\编辑于星期三3.6residuesperturnwithhydrogenbondsbetweenC’=OofresiduesnandNHofresiduesn+4.Theendofαhelicesarepolarandarealmostatthesurfaceofproteinmolecules现在是10页\一共有83页\编辑于星期三310helixπ

helix4.416helixN+53residuesperturnanda10atomsbetweenthehydrogenbonddonorandacceptor,N+3现在是11页\一共有83页\编辑于星期三Idealizedhelices:现在是12页\一共有83页\编辑于星期三Hydrogenbondingpatternsforfourhelices

273103.6134.414现在是13页\一共有83页\编辑于星期三现在是14页\一共有83页\编辑于星期三Theαhelixhasadipolemoment1.Theoveralleffectisasignificantnetdipolefortheαhelix.Thatgivesapartialpositivechargeattheaminoend

apartialnegativechargeattheCarboxylend(0.5-0.7unitcharge)2.Unitchargeateachendattractligandsofoppositecharge.PhosphategroupsfrequentlybindattheN-terminalofαhelix.Incontrast,positivechargeligandsrarelybindatC-teminal.现在是15页\一共有83页\编辑于星期三Someaminoacidsarepreferredinαhelix:Ala(A),Glu(E),Leu(L),andMet(M)

aregoodαhelicesformers.2)

Pro(P),Gly(G),Tyr(Y)andSer(S)

areveryPoorformers3)Themostcommonlocationforanαhelixinaproteinstructureisalongtheoutsideoftheprotein,withonesidefacingthesolutionandtheothersidefacingthehydrophobicinterioroftheprotein.4)αhelicesthatacrossmembranareinaHydrophobicenvironment,mostoftheirsideChainsarehydrophobic现在是16页\一共有83页\编辑于星期三现在是17页\一共有83页\编辑于星期三现在是18页\一共有83页\编辑于星期三Saccharomycescerevisiaemitochondrialthioredoxin3Baoetal.现在是19页\一共有83页\编辑于星期三MembraneProteinJ.Deisenhofer,H.MichelScience(245):1463,1989J.Dersenhofer,O.Epp,K.Miki,R.Huber,H.Michel,Nature(318):618,1985J.Deisenhofer,O.Epp,K.Miki,R.Huber,H.Michel,J.Mol.Biol.(180):385,1984H.MichelJ.Mol.Biol.(158):567,1982FirstMembraneProteinStructure:PhotosyntheticReactionCenterofRhodopseudomonasvirdis

红假单胞菌Complex(foursubunits)solvedin1985(1PRC)NobelChemistryPrizewasawardedtoJ.Deisenhofer,R.Huber,H.Michelin1988.现在是20页\一共有83页\编辑于星期三1)βsheet:

thebackboneofthepolypeptidechainisextendedintoa

zigzagstructure.2)

βsheet

isbuiltupfromacombinationofseveralregionsofthepolypeptidechain.3)Thelengthrangfrom5to10residues.β

sheet现在是21页\一共有83页\编辑于星期三现在是22页\一共有83页\编辑于星期三Theaminoacidecanallruninthesamebiochemicaldirection,amioterminaltocarboxyterminalTheaminoacidcanhavealternatingdirections,theN-terminaltoC-terminalfollowbyC-terminaltoN-terminal现在是23页\一共有83页\编辑于星期三Twoformshaveadistinctivepatternofhydrogen-bondingParallelAntiparallelTheβsheetthatareformedfromseveralβstrandsare

“pleated”现在是24页\一共有83页\编辑于星期三βsheetcanalsocombineintomixedβsheet(About20%ofknownproteinstructuresaremixed)现在是25页\一共有83页\编辑于星期三现在是26页\一共有83页\编辑于星期三Almostalltheβsheethavetwiststrands.This

twisthasthesamehandedness

(right-handed)φ,ψangleswithinthebroadstructurallyallowedregion现在是27页\一共有83页\编辑于星期三现在是28页\一共有83页\编辑于星期三theDouble-headedArrowheadProteaseInhibitorA

Baoetal.现在是29页\一共有83页\编辑于星期三现在是30页\一共有83页\编辑于星期三LoopregionfrequentlyparticipateinformingbindingsitesandenzymeactivesitesLoopregionsareatthesurfaceofproteinmoleculesHairpinloops现在是31页\一共有83页\编辑于星期三Hydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe4thaminogroupβ-turns:

connecttheendsoftwoadjacentsegmentsofanantiparallelβsheet.现在是32页\一共有83页\编辑于星期三现在是33页\一共有83页\编辑于星期三Productsof13genesinvolvedinpeptidyl-prolylcis-transisomeraseactivitythecommonpresenceofProandGlyresiduesinβturnsβ

turns现在是34页\一共有83页\编辑于星期三

γ

turnHydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe3rdaminogroup现在是35页\一共有83页\编辑于星期三ARamachandranplot现在是36页\一共有83页\编辑于星期三现在是37页\一共有83页\编辑于星期三SchematicpicturesofproteinshighlightsecondarystructureSimplifyFacilitateseeingsimilaritybetweenproteinsHelicessometimescylinders现在是38页\一共有83页\编辑于星期三TopologydiagramsareusefulforclassificationofproteinstructuresShowthedirectionofeachβstrandandthewaythestrandsareconnectedtoeachotheralongthepolypeptidechain现在是39页\一共有83页\编辑于星期三1,Thesecondarystructures2,Supersecondarystructuresanddomains

3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins现在是40页\一共有83页\编辑于星期三Supersecondarystructures,alsocalledmotifsorsimplyfolds,

areparticularlystablearrangementsofseveralelementsofsecondarystructureandtheconnectionsbetweenthem.现在是41页\一共有83页\编辑于星期三Twoαhelicesthatareconnectedbyashortloopregion.A:helix-turn-helixmotifisspecificforDNAbindingB:thecalciumbindingmotifispresentinmanyproteinsWhosefunctionisregulatedbycalcium.现在是42页\一共有83页\编辑于星期三Thecalcium-bindingmotifissymbolizedbyrighthandExample:thecalciumisboundtothemotifinthetroponin-CThecalcium-bindingmotifissymbolizedbyarighthand.ThismotifiscalledanEFhandbecausethefifthandsixthhelicesfromtheaminoterminusinstructureOfparavalbumin(inmusclerelaxationfoundin1973)whichalabeledEandF,arepartsofthestructurethatwereoriginalusedtoillustratecalciumbindingbythismotif.Theloopregionbetweenthetwoahelicesbindsthecalciumatom.CarboxylsidechainsfromAspandGlu,main-chainC’=OandH2Ofromligandstometalatom.Thehelix-loop-helixmotifprovidesascaffoldThatholdsthecalciumligandinproperpositiontobendandreleasecalcium.c)Thestructureoftroponin-CisbuiltupfromfourEFmotifs.现在是43页\一共有83页\编辑于星期三现在是44页\一共有83页\编辑于星期三Hairpinβmotif(Nospecificfunction)ThestrongpreferenceforβstrandstobeadjacentinβsheetswhentheyareadjacentintheaminoacidSequenceandthustoformahairpinβmotif.Thelengthoftheloopregionbetweentheβstrandsverybutaregenerallyfrom2to5residueslong.Thereisnospecificfunctionassociatedwiththismotif.现在是45页\一共有83页\编辑于星期三Twoexamples:a)bovintrypsininhibitor;b)snakevenomerabutoxin现在是46页\一共有83页\编辑于星期三TheGreekkeymotifExample:theenzymeStaphylococcusnuclease,anenzymethatdegradesDNATheGreekkeymotifisnotassociatedwithanyspecificfunction,Butitoccursfrequentlyinproteinstructures.

现在是47页\一共有83页\编辑于星期三The

β-α-βmotifcontainstwoparallelβstrandsThisloopisofteninvolvedinFormingthefunctionalbindingsite,oractivesite.Theloopregionscanbeofverydifferentlengths,from1or2residuestoover100.ThetwoloopshaveDifferentfunctions.Theloopthatconnectsthecarboxylendoftheβstrandwithaminoendofαhelixisofteninvolvedinformingthefunctionalbindingsite,oractivesite,ofthesestructures.Theseloopregionsthususuallyhaveconservedaminoacidsequencesinhomologousproteins.Incontrast,theotherloophasnotyetfoundtocontributetoanactivesite.现在是48页\一共有83页\编辑于星期三Connectionsbetweenβstrandsinlayeredβsheets现在是49页\一共有83页\编辑于星期三Twoarrangementsofβ

strandsstabilizedbythetendencyofthestrandstotwist.Hemolysin(apore-formingtoxinthatkillsacellbycreatingaholeinitsmembrane)fromthebacteriumStaphylococcusaureus(PDB7AHL).photolyase(aproteinthatrepairscertaintypesofDNAdamage)fromE.coli(PDB1DNP).现在是50页\一共有83页\编辑于星期三

氨基酸顺序相邻的花样通常在三维结构上也靠近

现在是51页\一共有83页\编辑于星期三RNA结合蛋白(ROP)的四个-螺旋折叠为一个四螺旋束

现在是52页\一共有83页\编辑于星期三

-螺旋的球状折叠

现在是53页\一共有83页\编辑于星期三

反平行的-链形成桶结构

现在是54页\一共有83页\编辑于星期三上-下--回折桶结构

现在是55页\一共有83页\编辑于星期三

反平行-结构中的希腊图案花样

现在是56页\一共有83页\编辑于星期三果冻卷饼状桶(jellyrollbarrels)

结构花样

现在是57页\一共有83页\编辑于星期三

/

TIM桶结构开放扭曲的/结构

现在是58页\一共有83页\编辑于星期三开放扭曲的α/β结构中的结合部位形成裂缝

现在是59页\一共有83页\编辑于星期三Proteinmoleculesareorganizedinastructuralhierarchy(等级）PrimarystructureSecondarystructureTertiarystructure(domains)Quaternarystructure现在是60页\一共有83页\编辑于星期三LargepolypeptidechainsfoldintoseveraldomainsEGF:domainsthatarehomologoustoepidermal(表皮细胞）growthfactor(53aminoacids)现在是61页\一共有83页\编辑于星期三Constructinglargemotifsfromsmallerones现在是62页\一共有83页\编辑于星期三1,re-visitofthesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins现在是63页\一共有83页\编辑于星期三Helpfulwebsites:1,PDB(ProteinDataBank)2,SCOP(StructuralClassificationofProteins)3,comparisonofproteinstructuresin3D现在是64页\一共有83页\编辑于星期三A,X-raycrystallographyB,NMR(nuclearmagneticresonance)C,CD(circulardichroism)D,…现在是65页\一共有83页\编辑于星期三Computerprograms现在是66页\一共有83页\编辑于星期三NMRandNobelPrice:1944:I.I.Rabi,suggeststhatinformationaboutatoms'nucleicanbeobtainedbystudyingtheinternalmagnetismofprotons.Thisformsthefundamentalbasisfortoday'sresonanceimagingtechnologies1952:

PhysicistsE.Purcell(Harvard)andF.Bloch(Stanford)discoverNuclearMagneticResonance(NMR).

1991:R.Ernst,AdvancesinNMRcouldleadtotheabilitytodirectlyobservethechemicalactionofmedicationinthebody.2002:JohnB.Fenn,KoichiTanaka,KurtWüthrichforthedevelopmentofnuclearmagneticresonancespectroscopyfordeterminingthethree-dimensionalstructureofbiologicalmacromoleculesinsolution"现在是67页\一共有83页\编辑于星期三

TheNobelPrizeinChemistry2002"forthedevelopmentofmethodsforidentificationandstructureanalysesofbiologicalmacromolecules""fortheirdevelopmentofsoftdesorptionionisationmethodsformassspectrometricanalysesofbiologicalmacromolecules""forhisdevelopmentofnuclearmagneticresonancespectroscopyfordeterminingthethree-dimensionalstructureofbiologicalmacromoleculesinsolution"

JohnB.Fenn

KoichiTanaka

KurtWüthrich

1/4oftheprize

1/4oftheprize

1/2oftheprizeUSAJapanSwitzerlandVirginiaCommonwealthUniversity

Richmond,VA,USAShimadzuCorp.

Kyoto,JapanEidgenössischeTechnischeHochschule(SwissFederalInstituteofTechnology)

Zurich,Switzerland;TheScrippsResearchInstitute

LaJolla,CA,USAb.1917b.1959b.1938现在是68页\一共有83页\编辑于星期三现在是69页\一共有83页\编辑于星期三现在是70页\一共有83页\编辑于星期三3Dstructurecomparison:

现在是71页\一共有83页\编辑于星期三1,re-visitofthesecondarystructures2,Toolstoinvestigatetheproteinconformation3,Supersecondarystructuresanddomains4,globularproteinsandSCOP5,fibrousproteins现在是72页\一共有83页\编辑于星期三Inconsideringthesehigherlevelsofstructure,itisusefultoclassifyproteinsintotwomajorgroups:fibrousproteins,havingpolypep