Interakce vazebných míst přirozených a mutovaných nikotinových receptorů s ligandy
Interactions of binding sites of wildtype and mutated nicotinic receptorswith ligands
dissertation thesis (DEFENDED)
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http://hdl.handle.net/20.500.11956/23661Identifiers
Study Information System: 87534
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- Kvalifikační práce [17857]
Faculty / Institute
Faculty of Science
Discipline
-
Department
Department of Physiology
Date of defense
27. 5. 2010
Publisher
Univerzita Karlova, Přírodovědecká fakultaLanguage
Czech
Grade
Pass
This work explorespropertiesof nicotinicacetylcholinereceptors' Nicotinicreceptorsarepentamerictransmembraneproteinswhichopentheir cationicchannelwhentheir bindingsites are occupiedby moleculesof agonists.Bindingsitesappearat the interfacebetweensubunitcr and a neighbouringsubunitif theirorderisappropriate'Bothofthesubunitsinteract withligand,subunita byit'sloopsA, B,c, theneighbouringsubunitbyloops D,E andpossiblyF.Lijandbindingleadstofar-reachingcfrangesofreceptor structurein manylevels,reportedarethemovementsof loopC butprobably alsoofloopF anda quatemarytwist.Receptor,whenactivated'canswitchto anon-conductingstateca||eddesensitized.Probabi|itiesofexistenceof differentreceptor-statescanbeinfluencedbysubstanceswhichbindeitherto the samesiteas agonist(competitiveeffect)or theyactfroma distinctsite (noncompetitive,allostericeffect)' Bymutatingwereplacednegativelychargedaminoacidsin F loopsof o andpsubunitsof receptorcr3B4by unchargedaminoacids'singlemutations crD192N,gE195Q,pE198OandBD200Ndidnothavesignificanteffectwhile BDlglNandBDlg2Northeircombinationaffectedthefunctionofreceptor. Activationcurvesofreceptorsmutatedinthesepositionswereshiftedto higer concentrationswhichis demonstratedon agonistsnicotineaneepibatidine' Receptorwithdoublemutationcouldbeactivatedonlybyepibatidinewithits ECava|ue...