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)詳解演示文稿當前第1頁\共有82頁\編于星期四\19點優(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)當前第2頁\共有82頁\編于星期四\19點1,thesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins當前第3頁\共有82頁\編于星期四\19點ProteinSecondaryStructure■Secondarystructureistheregulararrangementofaminoacidresiduesinasegmentofapolypeptidechain,inwhicheachresidueisspatiallyrelatedtoitsneighborsinthesameway.■Themostcommonsecondarystructuresaretheαhelix,theβ

conformation,andβ

turns.■Thesecondarystructureofapolypeptidesegmentcanbecompletelydefinediftheφand

ψanglesareknownforallaminoacidresiduesinthatsegment.當前第4頁\共有82頁\編于星期四\19點10papersfromLinusPaulingandcolleaguespublishedinPNAS,1951當前第5頁\共有82頁\編于星期四\19點αhelix310helixπ

helix:theoreticallypossible,butneverfoundintheproteins?sheet:parallelandanti-parallel當前第6頁\共有82頁\編于星期四\19點αhelix?sheet3.613helix當前第7頁\共有82頁\編于星期四\19點Parametersoffiveactualortheoreticalsecondarystructures:當前第8頁\共有82頁\編于星期四\19點αhelix:

thebackboneofthepolypeptidechainisextendedintohelicalstructureWhichIsbuiltupfromonecontinuousregion.αhelix當前第9頁\共有82頁\編于星期四\19點φ,ψanglepairapproximately-60°and-50°.Thelengthrangfrom4or5to44residues.Theaveragelengthisaround10residues

當前第10頁\共有82頁\編于星期四\19點3.6residuesperturnwithhydrogenbondsbetweenC’=OofresiduesnandNHofresiduesn+4.Theendofαhelicesarepolarandarealmostatthesurfaceofproteinmolecules當前第11頁\共有82頁\編于星期四\19點310helixπ

helix4.416helixN+53residuesperturnanda10atomsbetweenthehydrogenbonddonorandacceptor,N+3當前第12頁\共有82頁\編于星期四\19點Idealizedhelices:當前第13頁\共有82頁\編于星期四\19點Hydrogenbondingpatternsforfourhelices

273103.6134.414當前第14頁\共有82頁\編于星期四\19點當前第15頁\共有82頁\編于星期四\19點Theαhelixhasadipolemoment1.Theoveralleffectisasignificantnetdipolefortheαhelix.Thatgivesapartialpositivechargeattheaminoend

apartialnegativechargeattheCarboxylend(0.5-0.7unitcharge)2.Unitchargeateachendattractligandsofoppositecharge.PhosphategroupsfrequentlybindattheN-terminalofαhelix.Incontrast,positivechargeligandsrarelybindatC-teminal.當前第16頁\共有82頁\編于星期四\19點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當前第17頁\共有82頁\編于星期四\19點當前第18頁\共有82頁\編于星期四\19點當前第19頁\共有82頁\編于星期四\19點Saccharomycescerevisiaemitochondrialthioredoxin3Baoetal.當前第20頁\共有82頁\編于星期四\19點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.當前第21頁\共有82頁\編于星期四\19點1)βsheet:

thebackboneofthepolypeptidechainisextendedintoa

zigzagstructure.2)

βsheet

isbuiltupfromacombinationofseveralregionsofthepolypeptidechain.3)Thelengthrangfrom5to10residues.β

sheet當前第22頁\共有82頁\編于星期四\19點當前第23頁\共有82頁\編于星期四\19點Theaminoacidecanallruninthesamebiochemicaldirection,amioterminaltocarboxyterminalTheaminoacidcanhavealternatingdirections,theN-terminaltoC-terminalfollowbyC-terminaltoN-terminal當前第24頁\共有82頁\編于星期四\19點Twoformshaveadistinctivepatternofhydrogen-bondingParallelAntiparallelTheβsheetthatareformedfromseveralβstrandsare

“pleated”當前第25頁\共有82頁\編于星期四\19點βsheetcanalsocombineintomixedβsheet(About20%ofknownproteinstructuresaremixed)當前第26頁\共有82頁\編于星期四\19點當前第27頁\共有82頁\編于星期四\19點Almostalltheβsheethavetwiststrands.This

twisthasthesamehandedness

(right-handed)φ,ψangleswithinthebroadstructurallyallowedregion當前第28頁\共有82頁\編于星期四\19點當前第29頁\共有82頁\編于星期四\19點theDouble-headedArrowheadProteaseInhibitorA

Baoetal.當前第30頁\共有82頁\編于星期四\19點當前第31頁\共有82頁\編于星期四\19點LoopregionfrequentlyparticipateinformingbindingsitesandenzymeactivesitesLoopregionsareatthesurfaceofproteinmoleculesHairpinloops當前第32頁\共有82頁\編于星期四\19點Hydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe4thaminogroupβ-turns:

connecttheendsoftwoadjacentsegmentsofanantiparallelβsheet.當前第33頁\共有82頁\編于星期四\19點當前第34頁\共有82頁\編于星期四\19點Productsof13genesinvolvedinpeptidyl-prolylcis-transisomeraseactivitythecommonpresenceofProandGlyresiduesinβturnsβ

turns當前第35頁\共有82頁\編于星期四\19點

γ

turnHydrogenbondbetweentheoxygenof1stcarboxylgroupandhydrogenofthe3rdaminogroup當前第36頁\共有82頁\編于星期四\19點ARamachandranplot當前第37頁\共有82頁\編于星期四\19點當前第38頁\共有82頁\編于星期四\19點SchematicpicturesofproteinshighlightsecondarystructureSimplifyFacilitateseeingsimilaritybetweenproteinsHelicessometimescylinders當前第39頁\共有82頁\編于星期四\19點TopologydiagramsareusefulforclassificationofproteinstructuresShowthedirectionofeachβstrandandthewaythestrandsareconnectedtoeachotheralongthepolypeptidechain當前第40頁\共有82頁\編于星期四\19點1,Thesecondarystructures2,Supersecondarystructuresanddomains

3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins當前第41頁\共有82頁\編于星期四\19點Supersecondarystructures,alsocalledmotifsorsimplyfolds,

areparticularlystablearrangementsofseveralelementsofsecondarystructureandtheconnectionsbetweenthem.當前第42頁\共有82頁\編于星期四\19點Twoαhelicesthatareconnectedbyashortloopregion.A:helix-turn-helixmotifisspecificforDNAbindingB:thecalciumbindingmotifispresentinmanyproteinsWhosefunctionisregulatedbycalcium.當前第43頁\共有82頁\編于星期四\19點Thecalcium-bindingmotifissymbolizedbyrighthandExample:thecalciumisboundtothemotifinthetroponin-CThecalcium-bindingmotifissymbolizedbyarighthand.ThismotifiscalledanEFhandbecausethefifthandsixthhelicesfromtheaminoterminusinstructureOfparavalbumin(inmusclerelaxationfoundin1973)whichalabeledEandF,arepartsofthestructurethatwereoriginalusedtoillustratecalciumbindingbythismotif.Theloopregionbetweenthetwoahelicesbindsthecalciumatom.CarboxylsidechainsfromAspandGlu,main-chainC’=OandH2Ofromligandstometalatom.Thehelix-loop-helixmotifprovidesascaffoldThatholdsthecalciumligandinproperpositiontobendandreleasecalcium.c)Thestructureoftroponin-CisbuiltupfromfourEFmotifs.當前第44頁\共有82頁\編于星期四\19點當前第45頁\共有82頁\編于星期四\19點Hairpinβmotif(Nospecificfunction)ThestrongpreferenceforβstrandstobeadjacentinβsheetswhentheyareadjacentintheaminoacidSequenceandthustoformahairpinβmotif.Thelengthoftheloopregionbetweentheβstrandsverybutaregenerallyfrom2to5residueslong.Thereisnospecificfunctionassociatedwiththismotif.當前第46頁\共有82頁\編于星期四\19點Twoexamples:a)bovintrypsininhibitor;b)snakevenomerabutoxin當前第47頁\共有82頁\編于星期四\19點TheGreekkeymotifExample:theenzymeStaphylococcusnuclease,anenzymethatdegradesDNATheGreekkeymotifisnotassociatedwithanyspecificfunction,Butitoccursfrequentlyinproteinstructures.

當前第48頁\共有82頁\編于星期四\19點The

β-α-βmotifcontainstwoparallelβstrandsThisloopisofteninvolvedinFormingthefunctionalbindingsite,oractivesite.Theloopregionscanbeofverydifferentlengths,from1or2residuestoover100.ThetwoloopshaveDifferentfunctions.Theloopthatconnectsthecarboxylendoftheβstrandwithaminoendofαhelixisofteninvolvedinformingthefunctionalbindingsite,oractivesite,ofthesestructures.Theseloopregionsthususuallyhaveconservedaminoacidsequencesinhomologousproteins.Incontrast,theotherloophasnotyetfoundtocontributetoanactivesite.當前第49頁\共有82頁\編于星期四\19點Connectionsbetweenβstrandsinlayeredβsheets當前第50頁\共有82頁\編于星期四\19點Twoarrangementsofβ

strandsstabilizedbythetendencyofthestrandstotwist.Hemolysin(apore-formingtoxinthatkillsacellbycreatingaholeinitsmembrane)fromthebacteriumStaphylococcusaureus(PDB7AHL).photolyase(aproteinthatrepairscertaintypesofDNAdamage)fromE.coli(PDB1DNP).當前第51頁\共有82頁\編于星期四\19點

氨基酸順序相鄰的花樣通常在三維結(jié)構(gòu)上也靠近

當前第52頁\共有82頁\編于星期四\19點RNA結(jié)合蛋白(ROP)的四個-螺旋折疊為一個四螺旋束

當前第53頁\共有82頁\編于星期四\19點

-螺旋的球狀折疊

當前第54頁\共有82頁\編于星期四\19點

反平行的-鏈形成桶結(jié)構(gòu)

當前第55頁\共有82頁\編于星期四\19點上-下--回折桶結(jié)構(gòu)

當前第56頁\共有82頁\編于星期四\19點

反平行-結(jié)構(gòu)中的希臘圖案花樣

當前第57頁\共有82頁\編于星期四\19點果凍卷餅狀桶(jellyrollbarrels)

結(jié)構(gòu)花樣

當前第58頁\共有82頁\編于星期四\19點

/

TIM桶結(jié)構(gòu)開放扭曲的/結(jié)構(gòu)

當前第59頁\共有82頁\編于星期四\19點開放扭曲的α/β結(jié)構(gòu)中的結(jié)合部位形成裂縫

當前第60頁\共有82頁\編于星期四\19點Proteinmoleculesareorganizedinastructuralhierarchy(等級）PrimarystructureSecondarystructureTertiarystructure(domains)Quaternarystructure當前第61頁\共有82頁\編于星期四\19點LargepolypeptidechainsfoldintoseveraldomainsEGF:domainsthatarehomologoustoepidermal(表皮細胞）growthfactor(53aminoacids)當前第62頁\共有82頁\編于星期四\19點Constructinglargemotifsfromsmallerones當前第63頁\共有82頁\編于星期四\19點1,re-visitofthesecondarystructures2,Supersecondarystructuresanddomains3,Toolstoinvestigatetheproteinconformation4,globularproteinsandSCOP5,fibrousproteins當前第64頁\共有82頁\編于星期四\19點Helpfulwebsites:1,PDB(ProteinDataBank)2,SCOP(StructuralClassificationofProteins)3,comparisonofproteinstructuresin3D當前第65頁\共有82頁\編于星期四\19點A,X-raycrystallographyB,NMR(nuclearmagneticresonance)C,CD(circulardichroism)D,…當前第66頁\共有82頁\編于星期四\19點Computerprograms當前第67頁\共有82頁\編于星期四\19點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"當前第68頁\共有82頁\編于星期四\19點

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當前第69頁\共有82頁\編于星期四\19點當前第70頁\共有82頁\編于星期四\19點當前第71頁\共有82頁\編于星期四\19點3Dstructurecomparison:

當前第72頁\共有82頁\編于星期四\19點1,re-vis