Hauptseite > Publikationsdatenbank > Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process > print

001     19450
005     20240610120842.0
024 7 _ |2 pmid
|a pmid:22039220
024 7 _ |2 pmc
|a pmc:PMC3219140
024 7 _ |2 DOI
|a 10.1073/pnas.1015461108
024 7 _ |2 WOS
|a WOS:000297008900034
024 7 _ |a altmetric:433594
|2 altmetric
037 _ _ |a PreJuSER-19450
041 _ _ |a eng
082 _ _ |a 000
084 _ _ |2 WoS
|a Multidisciplinary Sciences
100 1 _ |0 P:(DE-HGF)0
|a Kirchberg, K.
|b 0
245 _ _ |a Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process
260 _ _ |a Washington, DC
|b Academy
|c 2011
300 _ _ |a 18690 - 18695
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |0 5100
|a Proceedings of the National Academy of Sciences of the United States of America
|v 108
|x 0027-8424
|y 46
500 _ _ |a We 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.).
520 _ _ |a Arrestins 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.
536 _ _ |0 G:(DE-Juel1)FUEK505
|2 G:(DE-HGF)
|a BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung
|c P45
|x 0
588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Animals
650 _ 2 |2 MeSH
|a Anisotropy
650 _ 2 |2 MeSH
|a Arrestin: chemistry
650 _ 2 |2 MeSH
|a Cattle
650 _ 2 |2 MeSH
|a Crystallography, X-Ray: methods
650 _ 2 |2 MeSH
|a Kinetics
650 _ 2 |2 MeSH
|a Microscopy, Fluorescence: methods
650 _ 2 |2 MeSH
|a Molecular Conformation
650 _ 2 |2 MeSH
|a Phosphorylation
650 _ 2 |2 MeSH
|a Protein Binding
650 _ 2 |2 MeSH
|a Protein Conformation
650 _ 2 |2 MeSH
|a Protein Structure, Tertiary
650 _ 2 |2 MeSH
|a Receptors, G-Protein-Coupled: chemistry
650 _ 2 |2 MeSH
|a Retina: metabolism
650 _ 2 |2 MeSH
|a Rhodopsin: chemistry
650 _ 2 |2 MeSH
|a Signal Transduction
650 _ 2 |2 MeSH
|a Spectrophotometry: methods
650 _ 7 |0 0
|2 NLM Chemicals
|a Arrestin
650 _ 7 |0 0
|2 NLM Chemicals
|a Receptors, G-Protein-Coupled
650 _ 7 |0 9009-81-8
|2 NLM Chemicals
|a Rhodopsin
650 _ 7 |2 WoSType
|a J
653 2 0 |2 Author
|a membrane receptor
653 2 0 |2 Author
|a protein conformational change
653 2 0 |2 Author
|a binding kinetics
700 1 _ |0 P:(DE-HGF)0
|a Kim, T.Y.
|b 1
700 1 _ |0 P:(DE-HGF)0
|a Möller, M.
|b 2
700 1 _ |0 P:(DE-HGF)0
|a Skegro, D.
|b 3
700 1 _ |0 P:(DE-Juel1)VDB102289
|a Raju, G.D.
|b 4
|u FZJ
700 1 _ |0 P:(DE-Juel1)131965
|a Granzin, J.
|b 5
|u FZJ
700 1 _ |0 P:(DE-Juel1)131957
|a Büldt, G.
|b 6
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB1421
|a Schlesinger, R.
|b 7
|u FZJ
700 1 _ |0 P:(DE-HGF)0
|a Alexiev, U.
|b 8
773 _ _ |0 PERI:(DE-600)1461794-8
|a 10.1073/pnas.1015461108
|g Vol. 108, p. 18690 - 18695
|p 18690 - 18695
|q 108<18690 - 18695
|t Proceedings of the National Academy of Sciences of the United States of America
|v 108
|x 0027-8424
|y 2011
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219140
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915 _ _ |0 StatID:(DE-HGF)0010
|a JCR/ISI refereed
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