bk通道β亚基loop区域对通道结构和功能影响

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1、华中科技大学博士学位论文theyproducedtheoutwardrectification.(2)β4subunitmainlyexpressesinnervoussystem,especiallyinbrainthatcanslowtheactivationanddeactivationofBKchannel.Currentlyknown,themostimportantnaturethatisbroughtbyβ4subunitistomakethechanneltoberesistantt

2、osomespecialtoxins,suchascharybdotoxin(CTX)andiberiotoxin(IbTX).Afterassociationwithβ4subunit,theblockrateofthetoxinreducesover1000timeandournervoussystemwillbekeptformdestroying.Throughexperiments,wediscovertheresistancetosometoxinrelatestoatyrosinein

3、uniquepositionandthreepositivechargedaminoacids.Thetyrosinein100orsoisthebindingsite.Toxincanbeeasilyclosetotheporeofchannelifthereissuchatyrosine.ThesequenceofCTXandIbTXarebothrichinpositivechargedaminoacids.Thepositivechargedaminoacidsinβ4loopsegment

4、andtoxinproducemutex,therebypreventingtoxinfromgettingneartotheporeofchannel.Becauseβ4subunithasnospecialtyrosinefortoxinbinding,itsabilityofresistingtoxinbecomesstronger.(3)Throughthetwoaboveexperiments,weknowloopsegmentofβsubunitswillforma“helmet”aft

5、erassociationwithαsubunitandbringBKchannelthestructuralandfunctionalchanges.Itisdifficulttogetcrystalstructureofionchannelproteinsatpresent.Soweapplycomputermodelingtoforecastthestructureoftheproteincomplex.Afteranalysis,wefindthatthelinkerbetweenS5tra

6、nsmembranesegmentandPore-loopdecentralizesfromthecenterwhenthereisnoβsubunitthatisdifferentfrompreviouspublishedKcsacrystalstructure.Followedbyassociationwithβsubunit,theS5-Plinkercentralizestowardtheporeofchannel.Afterformationofthecomplexstructure,th

7、reepositivechargedaminoacidslocatejustabovethemouthofthechannelandassistresisitingpositivechargedtoxins.Positivechargedaminoacidsofβ2subunitmigrateinsequence,comparedtoβ4subunit.Therefore,itsresistancetotoxinisweak.Butβ2subunitmakesBKchanneltoproduceou

8、twardrectification.Keywords：BKchannelβsubunitOutwardrectificationToxinblock独创性声明本人声明所呈交的学位论文是我个人在导师指导下进行的研究工作及取得的研究成果。尽我所知，除文中已经标明引用的内容外，本论文不包含任何其他个人或集体已经发表或撰写过的研究成果。对本文的研究做出贡献的个人和集体，均已在文中以明确方式标明。本人完全意识到本声明的法律结果由本人承担。学位论文作者签名：日期：年月日学位论文