蛋白質(zhì)的三維結(jié)構(gòu)蛋白質(zhì)三維結(jié)構(gòu)是由其氨基酸序列決定的；蛋白質(zhì)功能依賴其結(jié)構(gòu)，或結(jié)構(gòu)決定功能；一般來(lái)講，蛋白質(zhì)具有（接近）唯一確定的結(jié)構(gòu)；非共價(jià)相互作用是穩(wěn)定蛋白結(jié)構(gòu)的最主要因素；(疏水作用；氫鍵；離子鍵；VDW范德華…)在眾多蛋白質(zhì)結(jié)構(gòu)中，其折疊類型（fold）是有限的（2000個(gè)？）；研究蛋白結(jié)構(gòu)的方法（X光晶體學(xué)及核磁共振）；一些結(jié)構(gòu)與功能關(guān)系的例子……本章要點(diǎn)盡管蛋白質(zhì)結(jié)構(gòu)比較復(fù)雜，但仍然有許多規(guī)律。蛋白質(zhì)結(jié)構(gòu)研究得出的第一個(gè)基本規(guī)律是：親水表面疏水內(nèi)核水溶性球蛋白的折疊是將其疏水側(cè)鏈置于分子的內(nèi)部，產(chǎn)生一個(gè)“疏水內(nèi)核”和一個(gè)“親水表面”。蛋白質(zhì)分子的超二級(jí)結(jié)構(gòu)(花樣,motif)

若干二級(jí)結(jié)構(gòu)單元(secondarystructureelement)可以形成特殊的幾何組合出現(xiàn)在蛋白質(zhì)結(jié)構(gòu)中。這些由二級(jí)結(jié)構(gòu)依據(jù)特殊的幾何關(guān)系組合起來(lái)的結(jié)構(gòu)稱為超二級(jí)結(jié)構(gòu)(super-secondarystructure)或花樣(motif)。

超二級(jí)結(jié)構(gòu)（花樣）的存在，既可能與某些特殊的生物功能相關(guān)聯(lián)，也可能僅僅作為蛋白質(zhì)結(jié)構(gòu)的組裝模塊。

蛋白質(zhì)結(jié)構(gòu)中的若干個(gè)二級(jí)結(jié)構(gòu)和/或結(jié)構(gòu)花樣（motif）通常會(huì)依據(jù)特定的幾何位置排列形成較為致密的稱為“結(jié)構(gòu)域(domain)”的球形結(jié)構(gòu)。

三級(jí)結(jié)構(gòu)（tertiarystructure）作為常用的術(shù)語(yǔ)有兩重含義：其一，單條多肽鏈折疊形成的由一個(gè)或者多個(gè)結(jié)構(gòu)域組成的全部結(jié)構(gòu)；其二，二級(jí)結(jié)構(gòu)和/或結(jié)構(gòu)花樣排列形成的結(jié)構(gòu)域。蛋白質(zhì)分子的結(jié)構(gòu)域與三級(jí)結(jié)構(gòu)FromScience.2003Apr18;300(5618):445-52a/b

structuresSCOPstatisticsGraphicalrepresentationofproteinstructuresSomecrystalsfromSuLab,PekingUniversitySomestructuressolvedAK6(AD-004)NCC27HumanLMWPTP-BOXY-1Aβ-lactamaseBs803(YjbK)BsYflLBs47(HutI)Bs99(YjcG)LC1WRKY1-CSm35Sm32B.s.YwlESm23BsTim344KurtWüthrich1938Nobelpris2002Utvecklademetoderattstuderastrukturochdynamikavproteineril?sningmedNMREttprion—proteinetsomgergalnako-sjukanBeijingNMRCenterProteinFolding?a-helix–localinteractionb-sheet–longrangeinteractionHydrophoicresidues–proteincoreProteinFoldingAboutequilibriumofanyprocessorreaction.Whatdirectionwillprocessproceedtowardequilibrium?Howfarwillitgotowardcompletionbeforeitreachesequilibrium?Notabouthowitgetsthere.(e.g.howfastorwhatpathittakes)FirstLaw:Energyisconserved.SecondLaw:Disorderincreases.ThermodynamicsDG=DH–TDSDGischangeinGibbsFreeEnergy.Iftheendingstateislowerinfreeenergythanthestartingstate,reactionwillproceedspontaneously.DHischangeinEnthalpy.Enthalpyistheenergyfrombondsandattractiveinteractions.Negative

DHisfavorable.(e.g.formingmorebonds.)DSischangeinEntropy.Entropyisdisorder.PositiveDSisfavorable.(e.g.increasingtheamountofdisorder.)DirectionofBiochemicalProcessesStudiesoftheRNaseASmallproteinwith4disulfidebonds.Fact1:UreaUnfoldsProteinsFact2:b-mercaptoethanolbreaksdisulfidebondsStudiesoftheRNaseAStudiesoftheRNaseAInactiveRNasehadformed“wrong”disulfidebondswhileunfolded.Thewronglinkspreventedthepolypeptidechainfromattainingtheactiveconfigurationwhenureawasremoved.TheactiveribonucleasehadformedthecorrectdisulfidebondswhenbMEwasremoved.Thebackbonehadrefoldedcorrectly,priortoreoxidationIf“wrong”disulfidescouldbefixed,theactivityofinactiveRNasecouldberestored?StudiesoftheRNaseATraceofb-MEpresentwiththe"scrambled"RNasepermitteddisulfidebondstore-reduceandthenreoxidize,sonativeactivestructurecouldform.WhenrightcombinationsofS-Sbondsformed,theyremained,becausenativestructurewasthethermodynamicallymoststable(favored)state.StudiesoftheRNaseATheNobelPrizeinChemistry1972ChristianB.Anfinsen--forhisworkonribonuclease,especiallyconcerningtheconnectionbetweentheaminoacidsequenceandthebiologicallyactiveconformation"Thesequencedeterminesthestructure!Theinformationnecessarytospecifythestructureispresentinthesequence.Proteinsdonotsampleallpossibleconformations-rather,“partiallyfolded”states(“foldingintermediates”)withsomebutnotallpossiblebondsandinteractionsoccurduringthefoldingprocess.Thesequencealsospecifiesthefoldingpathway.Asmoreinteractionsform,thestructuregetscloserandclosertothefinalfoldedstate.Typicaltimesforproteinfoldingare~10-6secto102sec.ProteinFoldingPathwaysProteinFoldingPathwaysFreeEnergyLandscapeThecentraldogma中心法則FlowofinformationingeneexpressionThegeneticcodeThemRNAconsistsoffournucleotidesA,G,CandU.Threeconsecutivenucleotidesforma“codon”The64codonsencode20aminoacids,“Start”and“Stop”

SG’sfirsttask:Sequencethedomains(orfamilies)FromScience.2003Apr18;300(5618):445-52SCOPstatistics生物大分子結(jié)構(gòu)與功能的關(guān)系：

功能=運(yùn)動(dòng)著的結(jié)構(gòu)

生命是由蛋白復(fù)合物納米機(jī)器運(yùn)轉(zhuǎn)著Somesay:Functionisstructure!Otherssay:Structureisfunction!!Isay:Functionsarestructuresinmotion!!!TheribosometranslatesthemRNAsequenceintoproteinsequenceRamakrishnan(2002),Cell108,557-572

ThestructureofthelargeandsmallribosomalsubunitSchematicsurfacerepresentationwithanimation23SRNA:orange5SRNA:yellowproteins:blueActivesite:greenBan,Nissen,Hansen,Moore&Steitz(2000)Nissen,Hansen,Ban,Moore&Steitz(2000)TheElongationCyclestudiedbyCryo-EM13452EPARHowdo~100RNAhelicesin6RNA