biochemistry.docx
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biochemistry.docx
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biochemistry
Proteinmodificationanddegradation
蛋白质磷酸化
Proteinphosphorylationisapost-translationalmodificationofproteinsinwhichaserine,a
threonineoratyrosineresidueisphosphorylatedbyaproteinkinasebytheadditionofacovalentlyboundphosphategroup.
蛋白激酶(Proteinkinase,PK)
Aproteinkinaseisakinaseenzymethatmodifiesotherproteinsbychemicallyaddingphosphategroupstothem(phosphorylation).Phosphorylationusuallyresultsinafunctionalchangeofthetargetprotein(substrate)bychangingenzymeactivity,cellularlocation,orassociationwithotherproteins.
蛋白质磷酸化酶
Aphosphataseisanenzymethatremovesaphosphategroupfromitssubstratebyhydrolysingphosphoricacidmonoestersintoaphosphateionandamoleculewithafreehydroxylgroup.Thisreactionprocessisdephosphorylation.
蛋白质甲基化
ProteinMethylationistheadditionofamethylgroupsuppliedbySAMtoaproteincatalyzedbymethyltransferase.Methylationisaformofalkylationwithamethylgroup.Proteinmethylationtypicallytakesplaceonarginineorlysineaminoacidresiduesintheproteinsequence。
自噬
Autophagyisaprocessofself-digestionthatoccursineukaryoticcells.Autophagyinvolvestheformationofamembranearoundaregionofthecytoplasm,sequestering
macromoleculeslikeproteinsandorganelles,andthefusionoftheresultantvesiclewithalysosomeinwhichthecontentsaredegraded
蛋白质修饰加工包含哪些过程?
对蛋白质功能有何影响?
Posphorylation,lipidation14,methylation,acetylation,SUMOylation,
lysinecrotonylation,ubiquitination
1.Changethetargetproteinactivity;
2.Changeproteintranportation;
3.Changeproteinstability;
4.Changethetargetproteincellularlocation;
5.Changethetargetproteinassociationinteractionwithotherproteins.
自噬主要过程
(1)autophagyinductionandactivation(mTORC1、ULK/Atg1)
(2)sequestrationofcytoplasmandvesicleformation
Nucleation(becline1/Atg6、Vps34)extention(Atg12、Atg8/LC3)
(3)dockingandfusion
(4)breakdown
蛋白激酶的主要类型
Serine/threoninekinase
Tyrosine-specificproteinkinases
Histidine-specificproteinkinases
Dual-specificitykinase
泛素
Ubiquitinhasamolecularweightof8451andconsistsofasinglepolypeptidechaincontaining74aminoacidresidues,presentinginalleukaryoticorganismsinahighlyconservedform,whichfunctionstolabelharmful,defective,orsuperfluousproteinsfordegradationbytheproteasome.
比较SUMO化和泛素化
相同点:
SUMO化的反应途径类似,都具有活化,结合,连接三个过程。
不同点:
二者的功能完全不同
SUMO化的生物学作用:
增强蛋白质的稳定性。
(1)SUMO的核内底物多数都是转录调节因子或是共调节因子
(2)SUMO参与维持基因组的完整性及调节染色质凝集与分离
(3)SUMO参与DNA修复过程(4)SUMO可拮抗泛素的作用
(5)SUMO可调节蛋白的核质转运及信号转导
泛素化的生物学作用:
降解蛋白质。
调节多个细胞过程:
(1)调控细胞周期的正常运行
(2)调控细胞增殖
(3)调控细胞凋亡(4)细胞信号转导(5)调控细胞免疫和炎症反应
(6)调控肿瘤的恶化(7)调控基因转录(8)DNA的复制与修复
(9)维持正常的神经元的功能
组蛋白主要修饰方式
Acetylation、methylation、phosphorylation、ubiqutination、sumoylation
Protein-ProteinInteraction
蛋白质相互作用
Protein–proteininteractions(PPIs)refertointentionalphysicalcontactsestablishedbetweentwoormoreproteins(proteincomplex)asaresultofbiochemicaleventsand/orelectrostaticforces.
结构域
Proteininteractiondomainsisastructuretoallowtheirinteractionwithandbindtospecificsequencesonotherproteins.
相互作用组
Inmolecularbiology,aninteractomeisthewholesetofmolecularinteractionsinaparticularcell.Mostcommonly,interactomereferstoprotein–proteininteraction(PPI)network(PIN)orsubsetsthereof.
蛋白质相互作用的结构基础
1.PPI界面具有特征化学结构。
蛋白质结合部位之间构象能互补,而且具有相应的化学基团产生足够的结合力。
2.蛋白质具有相互作用识别的结构域
3.衔接蛋白和支架蛋白辅助蛋白质相互作用
主要结构域的功能
1SH2domain:
recognizepY
2SH3domain:
bindtoProlin-richpeptides
3WWdomain:
bindtoProlin-richpeptides
4PHdomain:
bindingPI
5PDZdomain:
bindingtheC-terminusofotherspecialproteins
6FHAdomain:
recognizepThr
7MH2domain:
bindingsite:
pSer
8bromodomain:
recognizemonoacetylatedlysineresidues
9Chromodomain:
bindmethylatedhistone
衔接蛋白
Adaptorproteincontainavarietyofprotein-bindingmodulesthatlinkprotein-bindingpartnerstogetherandfacilitatethecreationoflargersignalingcomplexes.Theseproteinstendtolackanyintrinsicenzymaticactivitythemselvesbutinsteadmediatespecificprotein–proteininteractionsthatdrivetheformationofproteincomplexes.
支架蛋白
Inbiology,scaffoldproteinsarecrucialregulatorsofmanykeysignalingpathways.Althoughscaffoldsarenotstrictlydefinedinfunction,theyareknowntointeractand/orbindwithmultiplemembersofasignalingpathway,tetheringthemintocomplexes.Insuchpathways,theyregulatesignaltransductionandhelplocalizepathwaycomponentstospecificareasofthecell.
如何设计实验证明A、B蛋白质相互作用
试验方法:
酵母双转染法(Yeasttwo-hybridscreening)
表达载体1:
GAL4-BD+bait(A)
Yeasttwo-hybridsystem表达载体2:
GAL4-AD+prey(B)
含有多个reportergene的菌株
若AB两种蛋白能相互作用,GAL4-BD与GAL4-AD能结合成有活性的转录因子,从而与reportergene的UAS结合,使reportergene得以表达,若能检测到reportergene的表达产物就证明AB两种蛋白相互作用
Proteomics
蛋白质组
Proteomeistheproteinsexpressedbyacellortissue,atagiventimeunderaspecificsetofconditions.
蛋白质组学
Proteomicsiscomprehensiveknowledgeaboutalltheproteinsofacellatagiventimeunderaspecialsetofcondition.Proteomicsisthelarge-scalestudyofproteins,particularlytheirstructuresandfunctions.
proteinfoldingandlocalization
蛋白质折叠
Proteinfoldingisaprocessofnascentpeptidechainfoldingtoformcorrectspatialconformation.
分子伴侣
Chaperoneisalargegroupofunrelatedproteinfamilieswhoseroleistostabilizeunfoldedproteins,unfoldthemfortranslocationacrossmembranesorfordegradation,and/ortoassistintheircorrectfoldingandassembly.
简述参与蛋白质折叠的辅助分子及其功能
Chaperone(stress-70family、chaperonin、triggerfactor)
Stabilizeunfoldedproteins、prohibitnon-naturalpolypeptidefrommisfoldingandaggregation.unfoldunfoldedproteinfortranslocationacrossmembranesorfordegradation,and/orassistintheircorrectfoldingandassembly
PDI(proteindisulfideisomerase)
TheyusuallycontainatleastoneCys-Xaa-Xaa-Cys(CXXC)activesitethatcancatalyzedisulfideformation,reduction,andisomerization.bybindingtonon-naturalprotein,PPIcan
prohibittheerroneousbindingandpolymerizationbetweentargetproteinandsubstrateprotein.
PPI(peptidylprolylcis-transisomerase)
catalysetheconversionofconformationbetweenthecis-isomerandthetans-isomer.
Intramolecularchaperone
ClassI(alphalyticproteinase):
Mainlyinvolvedinextendingandfoldingofthepolypeptidechain.
ClassII(somatostatinII):
Mainlyinvolvedinintracellulartransportandlocalization,notdirectlyinvolvedinproteinfolding,theleaderpeptidecontainsproteinsortinginformationwhichcanguidepropersecretionoftheprotein.
蛋白质靶向输送
Proteintargetingorproteinsortingisthebiologicalmechanismbywhichproteinsaretransportedtotheappropriatedestinationsinthecelloroutsideofit.Proteinscanbetargetedtotheinnerspaceofanorganelle,differentintracellularmembranes,plasmamembrane,ortoexteriorofthecellviasecretion.
靶向信号
Targetingsignalsarethepiecesofinformationthatenablethecellulartransportmachinerytocorrectlypositionaproteininsideoroutsidethecell.Thisinformationiscontainedinthepolypeptidechainorinthefoldedprotein.
信号肽
Thecontinuousstretchofaminoacidresiduesinthechainthatenablestargetingarecalledsignalpeptidesortargetingpeptides.
核定位信号
Anuclearlocalizationsignal(NLE)isashortsequenceconsistingof4-8aminoacidresiduesinaproteinandrichinpositivelychargedlysine,arginineandproline,whichtargetsproteinsfromthecytoplasmtothecellnucleusthroughthenuclearporecomplexusingnucleartransport.
核输出信号
Anuclearexportsignal(NES)isashortaminoacidsequenceof4hydrophobicresiduesinaproteinthattargetsitforexportfromthecellnucleustothecytoplasmthroughthenuclearporecomplexusingnucleartransport.
跨膜蛋白
Atransmembraneprotein(TP)spanfromonesideofamembranethroughtotheothersideofthemembrane.
I型跨膜蛋白/II型跨膜蛋白
GroupItransmembraneproteinshavetheirN-terminaldomainstargetedtheextracellularspaceGroupIItransmembraneproteinshavetheirC-terminaldomainstargetedtheextracellularspace.
有哪些大分子参与了新生肽链穿越内质网膜的过程?
Ribosome、Signalpeptide、SRP/SRPreceptor、
nucleoproteincomplex/nucleoproteincomplexreceptor、peptidetranslocationcomplex
举例说明蛋白质的定位和分拣机制?
信号肽介导蛋白质分子的定位和靶向运输
举例:
Ran-GTPnucleartransportcycle
胞质合成的细胞核蛋白的NSL被importinβ所识别,并与importinαβ二聚体结合成复合物,被引导到核膜和核孔;然后Ran-GTP水解GTP释能,胞核蛋白质-输入蛋白质复合物通过耗能机制跨核孔转位,进入核基质;最后转位过程中,importin的αβ亚基先后解离、移出核孔而被再利用。
蛋白质在核糖体被合成后经过哪些生化事件才变成成熟的蛋白质?
蛋白质的翻译后修饰、折叠、组装形成正确的空间构想,调节蛋白质的活性,蛋白质的定位和靶向运输
Signaltransduction
信号转导
Theintracellulartransferofinformation(biologicalactivation/inhibition)isthroughasignalpathway.theprocessiscalledsignaltransduction.Ineach signaltransduction system,anactivation/inhibitionsignalfromabiologicallyactivemolecule(hormone,neurotransmitter)ismediatedviathecouplingofareceptor/enzymetoasecondmessengersystemortoanionchannel. Signaltransduction playsanimportantroleinactivatingcellularfunctions,celldifferentiation,andcellproliferation.
第二信使
Secondmessengerisasubstancewhosereleasewithinacellispromotedbyahormoneor‘firstmessenger’,andwhichbringsaboutaresponsebythemomsecondmessengerconsistofcAMP、cGMP、IP3、DAGandCa2+
RTK(Receptorprotein-tyrosinekinase)
受体酪氨酸激酶(receptortyrosinekinase,RTK),是细胞表面一大类重要的受体家族。
所有的RTK都是由3个部分组成:
含有配体结合位点的细胞外结构域、单次跨膜的疏水α螺旋区、含有酪氨酸激酶活性的细胞内结构域。
它的胞外配体是可溶性或膜结合的多肽或蛋白类激素,包括胰岛素和多种生长因子,主要有表皮细胞生长因子(EGF)、血小板生长因子(PDGF)、巨噬细胞集落刺激因子(M-CSF)、胰岛素、类胰岛素生长因子-1(IGF-1)、肝细胞生长因子(HGF)、神经生长因子(NGF)和血管内皮生长因子(VEGF)等。
自身磷酸化
当配体与单跨膜螺旋受体结合后,催化型受体大多数发生二聚化,二聚体TPK的被激活,彼此可使对方的某些氨基酸残基磷酸化,这一过程称为自身磷酸化。
主要发生在TKR.
举例说明膜受体介导的信号转导通路
EGF/EGFR介导的RPTK-Ras-MAPK通
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