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000019450 0247_ $$2pmid$$apmid:22039220
000019450 0247_ $$2pmc$$apmc:PMC3219140
000019450 0247_ $$2DOI$$a10.1073/pnas.1015461108
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000019450 084__ $$2WoS$$aMultidisciplinary Sciences
000019450 1001_ $$0P:(DE-HGF)0$$aKirchberg, K.$$b0
000019450 245__ $$aConformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process
000019450 260__ $$aWashington, DC$$bAcademy$$c2011
000019450 300__ $$a18690 - 18695
000019450 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000019450 3367_ $$2BibTeX$$aARTICLE
000019450 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000019450 3367_ $$2DRIVER$$aarticle
000019450 440_0 $$05100$$aProceedings of the National Academy of Sciences of the United States of America$$v108$$x0027-8424$$y46
000019450 500__ $$aWe thank Dr. R. Batra Safferling (ICS) and C. Seidler (FU Berlin) for help with sample and measurements, and S. Lehmann for building up the light-scattering instrument. The work was supported by the Deutsche Forschungsgemeinschaft, Sfb 449, (to U.A.) and ONEXIM (to G.B.).
000019450 520__ $$aArrestins are regulatory molecules for G-protein coupled receptor function. In visual rhodopsin, selective binding of arrestin to the cytoplasmic side of light-activated, phosphorylated rhodopsin (P-Rh*) terminates signaling via the G-protein transducin. While the "phosphate-sensor" of arrestin for the recognition of receptor-attached phosphates is identified, the molecular mechanism of arrestin binding and the involvement of receptor conformations in this process are still largely hypothetic. Here we used fluorescence pump-probe and time-resolved fluorescence depolarization measurements to investigate the kinetics of arrestin conformational changes and the corresponding nanosecond dynamical changes at the receptor surface. We show that at least two sequential conformational changes of arrestin occur upon interaction with P-Rh*, thus providing a kinetic proof for the suggested multistep nature of arrestin binding. At the cytoplasmic surface of P-Rh*, the structural dynamics of the amphipathic helix 8 (H8), connecting transmembrane helix 7 and the phosphorylated C-terminal tail, depends on the arrestin interaction state. We find that a high mobility of H8 is required in the low-affinity (prebinding) but not in the high-affinity binding state. High-affinity arrestin binding is inhibited when a bulky, inflexible group is bound to H8, indicating close interaction. We further show that this close steric interaction of H8 with arrestin is mandatory for the transition from prebinding to high-affinity binding; i.e., for arrestin activation. This finding implies a regulatory role for H8 in activation of visual arrestin, which shows high selectivity to P-Rh* in contrast to the broad receptor specificity displayed by the two nonvisual arrestins.
000019450 536__ $$0G:(DE-Juel1)FUEK505$$2G:(DE-HGF)$$aBioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung$$cP45$$x0
000019450 588__ $$aDataset connected to Web of Science, Pubmed
000019450 65320 $$2Author$$amembrane receptor
000019450 65320 $$2Author$$aprotein conformational change
000019450 65320 $$2Author$$abinding kinetics
000019450 650_2 $$2MeSH$$aAnimals
000019450 650_2 $$2MeSH$$aAnisotropy
000019450 650_2 $$2MeSH$$aArrestin: chemistry
000019450 650_2 $$2MeSH$$aCattle
000019450 650_2 $$2MeSH$$aCrystallography, X-Ray: methods
000019450 650_2 $$2MeSH$$aKinetics
000019450 650_2 $$2MeSH$$aMicroscopy, Fluorescence: methods
000019450 650_2 $$2MeSH$$aMolecular Conformation
000019450 650_2 $$2MeSH$$aPhosphorylation
000019450 650_2 $$2MeSH$$aProtein Binding
000019450 650_2 $$2MeSH$$aProtein Conformation
000019450 650_2 $$2MeSH$$aProtein Structure, Tertiary
000019450 650_2 $$2MeSH$$aReceptors, G-Protein-Coupled: chemistry
000019450 650_2 $$2MeSH$$aRetina: metabolism
000019450 650_2 $$2MeSH$$aRhodopsin: chemistry
000019450 650_2 $$2MeSH$$aSignal Transduction
000019450 650_2 $$2MeSH$$aSpectrophotometry: methods
000019450 650_7 $$00$$2NLM Chemicals$$aArrestin
000019450 650_7 $$00$$2NLM Chemicals$$aReceptors, G-Protein-Coupled
000019450 650_7 $$09009-81-8$$2NLM Chemicals$$aRhodopsin
000019450 650_7 $$2WoSType$$aJ
000019450 7001_ $$0P:(DE-HGF)0$$aKim, T.Y.$$b1
000019450 7001_ $$0P:(DE-HGF)0$$aMöller, M.$$b2
000019450 7001_ $$0P:(DE-HGF)0$$aSkegro, D.$$b3
000019450 7001_ $$0P:(DE-Juel1)VDB102289$$aRaju, G.D.$$b4$$uFZJ
000019450 7001_ $$0P:(DE-Juel1)131965$$aGranzin, J.$$b5$$uFZJ
000019450 7001_ $$0P:(DE-Juel1)131957$$aBüldt, G.$$b6$$uFZJ
000019450 7001_ $$0P:(DE-Juel1)VDB1421$$aSchlesinger, R.$$b7$$uFZJ
000019450 7001_ $$0P:(DE-HGF)0$$aAlexiev, U.$$b8
000019450 773__ $$0PERI:(DE-600)1461794-8$$a10.1073/pnas.1015461108$$gVol. 108, p. 18690 - 18695$$p18690 - 18695$$q108<18690 - 18695$$tProceedings of the National Academy of Sciences of the United States of America$$v108$$x0027-8424$$y2011
000019450 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219140
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000019450 915__ $$0StatID:(DE-HGF)0010$$aJCR/ISI refereed
000019450 9141_ $$y2011
000019450 9131_ $$0G:(DE-Juel1)FUEK505$$aDE-HGF$$bSchlüsseltechnologien$$kP45$$lBiologische Informationsverarbeitung$$vBioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung$$x0
000019450 9132_ $$0G:(DE-HGF)POF3-551$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$aDE-HGF$$bKey Technologies$$lBioSoft  Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vFunctional Macromolecules and Complexes$$x0
000019450 9201_ $$0I:(DE-Juel1)ICS-5-20110106$$gICS$$kICS-5$$lMolekulare Biophysik$$x0
000019450 9201_ $$0I:(DE-Juel1)ICS-6-20110106$$gICS$$kICS-6$$lStrukturbiochemie$$x1
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