生物大分子結(jié)構(gòu)與功能相互作用力詳解演示文稿

生物大分子結(jié)構(gòu)與功能相互作用力第節(jié)第節(jié)詳解演示文稿目前一頁\總數(shù)八十二頁\編于二十點(diǎn)優(yōu)選生物大分子結(jié)構(gòu)與功能相互作用力第節(jié)第節(jié)目前二頁\總數(shù)八十二頁\編于二十點(diǎn)1,thesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins目前三頁\總數(shù)八十二頁\編于二十點(diǎn)ProteinSecondaryStructure■Secondarystructureistheregulararrangementofaminoacidresiduesinasegmentofapolypeptidechain,inwhicheachresidueisspatiallyrelatedtoitsneighborsinthesameway.■Themostcommonsecondarystructuresaretheαhelix,theβ

conformation,andβ

turns.■Thesecondarystructureofapolypeptidesegmentcanbecompletelydefinediftheφand

ψanglesareknownforallaminoacidresiduesinthatsegment.目前四頁\總數(shù)八十二頁\編于二十點(diǎn)10papersfromLinusPaulingandcolleaguespublishedinPNAS,1951目前五頁\總數(shù)八十二頁\編于二十點(diǎn)αhelix310helixπ

helix:theoreticallypossible,butneverfoundintheproteins?sheet:parallelandanti-parallel目前六頁\總數(shù)八十二頁\編于二十點(diǎn)αhelix?sheet3.613helix目前七頁\總數(shù)八十二頁\編于二十點(diǎn)Parametersoffiveactualortheoreticalsecondarystructures:目前八頁\總數(shù)八十二頁\編于二十點(diǎn)αhelix:

thebackboneofthepolypeptidechainisextendedintohelicalstructureWhichIsbuiltupfromonecontinuousregion.αhelix目前九頁\總數(shù)八十二頁\編于二十點(diǎn)φ,ψanglepairapproximately-60°and-50°.Thelengthrangfrom4or5to44residues.Theaveragelengthisaround10residues

目前十頁\總數(shù)八十二頁\編于二十點(diǎn)3.6residuesperturnwithhydrogenbondsbetweenC’=OofresiduesnandNHofresiduesn+4.Theendofαhelicesarepolarandarealmostatthesurfaceofproteinmolecules目前十一頁\總數(shù)八十二頁\編于二十點(diǎn)310helixπ

helix4.416helixN+53residuesperturnanda10atomsbetweenthehydrogenbonddonorandacceptor,N+3目前十二頁\總數(shù)八十二頁\編于二十點(diǎn)Idealizedhelices:目前十三頁\總數(shù)八十二頁\編于二十點(diǎn)Hydrogenbondingpatternsforfourhelices

273103.6134.414目前十四頁\總數(shù)八十二頁\編于二十點(diǎn)目前十五頁\總數(shù)八十二頁\編于二十點(diǎn)Theαhelixhasadipolemoment1.Theoveralleffectisasignificantnetdipolefortheαhelix.Thatgivesapartialpositivechargeattheaminoend

apartialnegativechargeattheCarboxylend(0.5-0.7unitcharge)2.Unitchargeateachendattractligandsofoppositecharge.PhosphategroupsfrequentlybindattheN-terminalofαhelix.Incontrast,positivechargeligandsrarelybindatC-teminal.目前十六頁\總數(shù)八十二頁\編于二十點(diǎn)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目前十七頁\總數(shù)八十二頁\編于二十點(diǎn)目前十八頁\總數(shù)八十二頁\編于二十點(diǎn)目前十九頁\總數(shù)八十二頁\編于二十點(diǎn)Saccharomycescerevisiaemitochondrialthioredoxin3Baoetal.目前二十頁\總數(shù)八十二頁\編于二十點(diǎn)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

紅假單胞菌Complex(foursubunits)solvedin1985(1PRC)NobelChemistryPrizewasawardedtoJ.Deisenhofer,R.Huber,H.Michelin1988.目前二十一頁\總數(shù)八十二頁\編于二十點(diǎn)1)βsheet:

thebackboneofthepolypeptidechainisextendedintoa

zigzagstructure.2)

βsheet

isbuiltupfromacombinationofseveralregionsofthepolypeptidechain.3)Thelengthrangfrom5to10residues.β

sheet目前二十二頁\總數(shù)八十二頁\編于二十點(diǎn)目前二十三頁\總數(shù)八十二頁\編于二十點(diǎn)Theaminoacidecanallruninthesamebiochemicaldirection,amioterminaltocarboxyterminalTheaminoacidcanhavealternatingdirections,theN-terminaltoC-terminalfollowbyC-terminaltoN-terminal目前二十四頁\總數(shù)八十二頁\編于二十點(diǎn)Twoformshaveadistinctivepatternofhydrogen-bondingParallelAntiparallelTheβsheetthatareformedfromseveralβstrandsare

“pleated”目前二十五頁\總數(shù)八十二頁\編于二十點(diǎn)βsheetcanalsocombineintomixedβsheet(About20%ofknownproteinstructuresaremixed)目前二十六頁\總數(shù)八十二頁\編于二十點(diǎn)目前二十七頁\總數(shù)八十二頁\編于二十點(diǎn)Almostalltheβsheethavetwiststrands.This

twisthasthesamehandedness

(right-handed)φ,ψangleswithinthebroadstructurallyallowedregion目前二十八頁\總數(shù)八十二頁\編于二十點(diǎn)目前二十九頁\總數(shù)八十二頁\編于二十點(diǎn)theDouble-headedArrowheadProteaseInhibitorA

Baoetal.目前三十頁\總數(shù)八十二頁\編于二十點(diǎn)目前三十一頁\總數(shù)八十二頁\編于二十點(diǎn)LoopregionfrequentlyparticipateinformingbindingsitesandenzymeactivesitesLoopregionsareatthesurfaceofproteinmoleculesHairpinloops目前三十二頁\總數(shù)八十二頁\編于二十點(diǎn)Hydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe4thaminogroupβ-turns:

connecttheendsoftwoadjacentsegmentsofanantiparallelβsheet.目前三十三頁\總數(shù)八十二頁\編于二十點(diǎn)目前三十四頁\總數(shù)八十二頁\編于二十點(diǎn)Productsof13genesinvolvedinpeptidyl-prolylcis-transisomeraseactivitythecommonpresenceofProandGlyresiduesinβturnsβ

turns目前三十五頁\總數(shù)八十二頁\編于二十點(diǎn)

γ

turnHydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe3rdaminogroup目前三十六頁\總數(shù)八十二頁\編于二十點(diǎn)ARamachandranplot目前三十七頁\總數(shù)八十二頁\編于二十點(diǎn)目前三十八頁\總數(shù)八十二頁\編于二十點(diǎn)SchematicpicturesofproteinshighlightsecondarystructureSimplifyFacilitateseeingsimilaritybetweenproteinsHelicessometimescylinders目前三十九頁\總數(shù)八十二頁\編于二十點(diǎn)TopologydiagramsareusefulforclassificationofproteinstructuresShowthedirectionofeachβstrandandthewaythestrandsareconnectedtoeachotheralongthepolypeptidechain目前四十頁\總數(shù)八十二頁\編于二十點(diǎn)1,Thesecondarystructures2,Supersecondarystructuresanddomains

3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins目前四十一頁\總數(shù)八十二頁\編于二十點(diǎn)Supersecondarystructures,alsocalledmotifsorsimplyfolds,

areparticularlystablearrangementsofseveralelementsofsecondarystructureandtheconnectionsbetweenthem.目前四十二頁\總數(shù)八十二頁\編于二十點(diǎn)Twoαhelicesthatareconnectedbyashortloopregion.A:helix-turn-helixmotifisspecificforDNAbindingB:thecalciumbindingmotifispresentinmanyproteinsWhosefunctionisregulatedbycalcium.目前四十三頁\總數(shù)八十二頁\編于二十點(diǎn)Thecalcium-bindingmotifissymbolizedbyrighthandExample:thecalciumisboundtothemotifinthetroponin-CThecalcium-bindingmotifissymbolizedbyarighthand.ThismotifiscalledanEFhandbecausethefifthandsixthhelicesfromtheaminoterminusinstructureOfparavalbumin(inmusclerelaxationfoundin1973)whichalabeledEandF,arepartsofthestructurethatwereoriginalusedtoillustratecalciumbindingbythismotif.Theloopregionbetweenthetwoahelicesbindsthecalciumatom.CarboxylsidechainsfromAspandGlu,main-chainC’=OandH2Ofromligandstometalatom.Thehelix-loop-helixmotifprovidesascaffoldThatholdsthecalciumligandinproperpositiontobendandreleasecalcium.c)Thestructureoftroponin-CisbuiltupfromfourEFmotifs.目前四十四頁\總數(shù)八十二頁\編于二十點(diǎn)目前四十五頁\總數(shù)八十二頁\編于二十點(diǎn)Hairpinβmotif(Nospecificfunction)ThestrongpreferenceforβstrandstobeadjacentinβsheetswhentheyareadjacentintheaminoacidSequenceandthustoformahairpinβmotif.Thelengthoftheloopregionbetweentheβstrandsverybutaregenerallyfrom2to5residueslong.Thereisnospecificfunctionassociatedwiththismotif.目前四十六頁\總數(shù)八十二頁\編于二十點(diǎn)Twoexamples:a)bovintrypsininhibitor;b)snakevenomerabutoxin目前四十七頁\總數(shù)八十二頁\編于二十點(diǎn)TheGreekkeymotifExample:theenzymeStaphylococcusnuclease,anenzymethatdegradesDNATheGreekkeymotifisnotassociatedwithanyspecificfunction,Butitoccursfrequentlyinproteinstructures.

目前四十八頁\總數(shù)八十二頁\編于二十點(diǎn)The

β-α-βmotifcontainstwoparallelβstrandsThisloopisofteninvolvedinFormingthefunctionalbindingsite,oractivesite.Theloopregionscanbeofverydifferentlengths,from1or2residuestoover100.ThetwoloopshaveDifferentfunctions.Theloopthatconnectsthecarboxylendoftheβstrandwithaminoendofαhelixisofteninvolvedinformingthefunctionalbindingsite,oractivesite,ofthesestructures.Theseloopregionsthususuallyhaveconservedaminoacidsequencesinhomologousproteins.Incontrast,theotherloophasnotyetfoundtocontributetoanactivesite.目前四十九頁\總數(shù)八十二頁\編于二十點(diǎn)Connectionsbetweenβstrandsinlayeredβsheets目前五十頁\總數(shù)八十二頁\編于二十點(diǎn)Twoarrangementsofβ

strandsstabilizedbythetendencyofthestrandstotwist.Hemolysin(apore-formingtoxinthatkillsacellbycreatingaholeinitsmembrane)fromthebacteriumStaphylococcusaureus(PDB7AHL).photolyase(aproteinthatrepairscertaintypesofDNAdamage)fromE.coli(PDB1DNP).目前五十一頁\總數(shù)八十二頁\編于二十點(diǎn)

氨基酸順序相鄰的花樣通常在三維結(jié)構(gòu)上也靠近

目前五十二頁\總數(shù)八十二頁\編于二十點(diǎn)RNA結(jié)合蛋白(ROP)的四個(gè)-螺旋折疊為一個(gè)四螺旋束

目前五十三頁\總數(shù)八十二頁\編于二十點(diǎn)

-螺旋的球狀折疊

目前五十四頁\總數(shù)八十二頁\編于二十點(diǎn)

反平行的-鏈形成桶結(jié)構(gòu)

目前五十五頁\總數(shù)八十二頁\編于二十點(diǎn)上-下--回折桶結(jié)構(gòu)

目前五十六頁\總數(shù)八十二頁\編于二十點(diǎn)

反平行-結(jié)構(gòu)中的希臘圖案花樣

目前五十七頁\總數(shù)八十二頁\編于二十點(diǎn)果凍卷餅狀桶(jellyrollbarrels)

結(jié)構(gòu)花樣

目前五十八頁\總數(shù)八十二頁\編于二十點(diǎn)

/

TIM桶結(jié)構(gòu)開放扭曲的/結(jié)構(gòu)

目前五十九頁\總數(shù)八十二頁\編于二十點(diǎn)開放扭曲的α/β結(jié)構(gòu)中的結(jié)合部位形成裂縫

目前六十頁\總數(shù)八十二頁\編于二十點(diǎn)Proteinmoleculesareorganizedinastructuralhierarchy(等級(jí)）PrimarystructureSecondarystructureTertiarystructure(domains)Quaternarystructure目前六十一頁\總數(shù)八十二頁\編于二十點(diǎn)LargepolypeptidechainsfoldintoseveraldomainsEGF:domainsthatarehomologoustoepidermal(表皮細(xì)胞）growthfactor(53aminoacids)目前六十二頁\總數(shù)八十二頁\編于二十點(diǎn)Constructinglargemotifsfromsmallerones目前六十三頁\總數(shù)八十二頁\編于二十點(diǎn)1,re-visitofthesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins目前六十四頁\總數(shù)八十二頁\編于二十點(diǎn)Helpfulwebsites:1,PDB(ProteinDataBank)2,SCOP(StructuralClassificationofProteins)3,comparisonofproteinstructuresin3D目前六十五頁\總數(shù)八十二頁\編于二十點(diǎn)A,X-raycrystallographyB,NMR(nuclearmagneticresonance)C,CD(circulardichroism)D,…目前六十六頁\總數(shù)八十二頁\編于二十點(diǎn)Computerprograms目前六十七頁\總數(shù)八十二頁\編于二十點(diǎn)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"目前六十八頁\總數(shù)八十二頁\編于二十點(diǎn)

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

JohnB.Fenn

KoichiTanaka

KurtWüthrich

1/4oftheprize

1/4oftheprize

1/2oftheprizeUSAJapanSwitzerlandVirginiaCommonwealthUniversity

Richmond,VA,USAShimadzuCorp.

Kyoto,JapanEidgen?ssischeTechnischeHochschule(SwissFederalInstituteofTechnology)

Zurich,Switzerland;TheScrippsResearchInstitute

LaJolla,CA,USAb.1917b.1959b.1938目前六十九頁\總數(shù)八十二頁\編于二十點(diǎn)目前七十頁\總數(shù)八十二頁\編于二十點(diǎn)目前七十一頁\總數(shù)八十二頁\編于二十點(diǎn)3Dstructurecomparison:

目前七十二頁\總數(shù)八十二頁\編于二十點(diǎn)1,re