000829376 001__ 829376
000829376 005__ 20240625095127.0
000829376 0247_ $$2doi$$a10.1038/srep45761
000829376 0247_ $$2Handle$$a2128/14205
000829376 0247_ $$2WOS$$aWOS:000398321200001
000829376 0247_ $$2altmetric$$aaltmetric:18485991
000829376 0247_ $$2pmid$$apmid:28368046
000829376 037__ $$aFZJ-2017-03089
000829376 041__ $$aEnglish
000829376 082__ $$a000
000829376 1001_ $$0P:(DE-HGF)0$$aSena, Diniz M.$$b0
000829376 245__ $$aStructural heterogeneity of the $μ$-opioid receptor’s conformational ensemble in the apo state
000829376 260__ $$aLondon$$bNature Publishing Group$$c2017
000829376 3367_ $$2DRIVER$$aarticle
000829376 3367_ $$2DataCite$$aOutput Types/Journal article
000829376 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1492516563_26745
000829376 3367_ $$2BibTeX$$aARTICLE
000829376 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000829376 3367_ $$00$$2EndNote$$aJournal Article
000829376 520__ $$aG-protein coupled receptors (GPCRs) are the largest and most pharmaceutically relevant family of membrane proteins. Here, fully unbiased, enhanced sampling simulations of a constitutively active mutant (CAM) of a class A GPCR, the μ-opioid receptor (μOR), demonstrates repeated transitions between the inactive (IS) and active-like (AS-L) states. The interconversion features typical activation/inactivation patterns involving established conformational rearrangements of conserved residues. By contrast, wild-type μOR remains in IS during the same course of simulation, consistent with the low basal activity of the protein. The simulations point to an important role of residue W2936.48 at the “toggle switch” in the mutation-induced constitutive activation. Such role has been already observed for other CAMs of class A GPCRs. We also find a significantly populated intermediate state, rather similar to IS. Based on the remarkable accord between simulations and experiments, we suggest here that this state, which has escaped so far experimental characterization, might constitute an early step in the activation process of the apo μOR CAM.
000829376 536__ $$0G:(DE-HGF)POF3-572$$a572 - (Dys-)function and Plasticity (POF3-572)$$cPOF3-572$$fPOF III$$x0
000829376 588__ $$aDataset connected to CrossRef
000829376 7001_ $$0P:(DE-HGF)0$$aCong, Xiaojing$$b1$$eCorresponding author
000829376 7001_ $$0P:(DE-Juel1)165199$$aGiorgetti, Alejandro$$b2$$ufzj
000829376 7001_ $$0P:(DE-HGF)0$$aKless, Achim$$b3
000829376 7001_ $$0P:(DE-Juel1)145614$$aCarloni, Paolo$$b4$$eCorresponding author
000829376 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/srep45761$$gVol. 8, p. 45761 -$$p45761 $$tScientific reports$$v7$$x2045-2322$$y2017
000829376 8564_ $$uhttps://juser.fz-juelich.de/record/829376/files/srep45761.pdf$$yOpenAccess
000829376 8564_ $$uhttps://juser.fz-juelich.de/record/829376/files/srep45761.gif?subformat=icon$$xicon$$yOpenAccess
000829376 8564_ $$uhttps://juser.fz-juelich.de/record/829376/files/srep45761.jpg?subformat=icon-1440$$xicon-1440$$yOpenAccess
000829376 8564_ $$uhttps://juser.fz-juelich.de/record/829376/files/srep45761.jpg?subformat=icon-180$$xicon-180$$yOpenAccess
000829376 8564_ $$uhttps://juser.fz-juelich.de/record/829376/files/srep45761.jpg?subformat=icon-640$$xicon-640$$yOpenAccess
000829376 8564_ $$uhttps://juser.fz-juelich.de/record/829376/files/srep45761.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000829376 8767_ $$82676048997$$92017-04-14$$d2017-07-25$$eAPC$$jZahlung erfolgt$$pSREP-16-41839A
000829376 909CO $$ooai:juser.fz-juelich.de:829376$$pdnbdelivery$$popenCost$$pVDB$$pdriver$$pOpenAPC$$popen_access$$popenaire
000829376 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145614$$aForschungszentrum Jülich$$b4$$kFZJ
000829376 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145614$$aForschungszentrum Jülich$$b4$$kFZJ
000829376 9131_ $$0G:(DE-HGF)POF3-572$$1G:(DE-HGF)POF3-570$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lDecoding the Human Brain$$v(Dys-)function and Plasticity$$x0
000829376 9141_ $$y2017
000829376 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000829376 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000829376 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000829376 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record
000829376 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bSCI REP-UK : 2015
000829376 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bSCI REP-UK : 2015
000829376 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal
000829376 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ
000829376 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000829376 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000829376 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000829376 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000829376 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences
000829376 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000829376 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000829376 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000829376 920__ $$lyes
000829376 9201_ $$0I:(DE-Juel1)IAS-5-20120330$$kIAS-5$$lComputational Biomedicine$$x0
000829376 9201_ $$0I:(DE-Juel1)INM-9-20140121$$kINM-9$$lComputational Biomedicine$$x1
000829376 9801_ $$aFullTexts
000829376 980__ $$ajournal
000829376 980__ $$aVDB
000829376 980__ $$aUNRESTRICTED
000829376 980__ $$aI:(DE-Juel1)IAS-5-20120330
000829376 980__ $$aI:(DE-Juel1)INM-9-20140121
000829376 980__ $$aAPC