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PMID: 22579250 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Conformational dynamics of activation for the pentameric complex of dimeric G protein-coupled receptor and heterotrimeric G protein.

Structure (London, England : 1993) ·Vol. 20 ·No. 5 ·2012-05-09 ·Pages 826-40

Orban T, Jastrzebska B, Gupta S, Wang B, Miyagi M, Chance MR, Palczewski K

Abstract

Photoactivation of rhodopsin (Rho), a G protein-coupled receptor, causes conformational changes that provide a specific binding site for the rod G protein, G(t). In this work we employed structural mass spectrometry techniques to elucidate the structural changes accompanying transition of ground state Rho to photoactivated Rho (Rho(∗)) and in the pentameric complex between dimeric Rho(∗) and heterotrimeric G(t). Observed differences in hydroxyl radical labeling and deuterium uptake between Rho(∗) and the (Rho(∗))(2)-G(t) complex suggest that photoactivation causes structural relaxation of Rho following its initial tightening upon G(t) coupling. In contrast, nucleotide-free G(t) in the complex is significantly more accessible to deuterium uptake allowing it to accept GTP and mediating complex dissociation. Thus, we provide direct evidence that in the critical step of signal amplification, Rho(∗) and G(t) exhibit dissimilar conformational changes when they are coupled in the (Rho(∗))(2)-G(t) complex.

MeSH Terms
Animals Binding Sites Cattle Heterotrimeric GTP-Binding Proteins/chemistry Light Models, Molecular Protein Conformation Protein Multimerization Receptors, G-Protein-Coupled/chemistry,metabolism Rhodopsin/chemistry,metabolism
Chemicals
Receptors, G-Protein-Coupled Rhodopsin Heterotrimeric GTP-Binding Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Orban Tivadar
Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4988, USA.
Jastrzebska Beata
Gupta Sayan
Wang Benlian
Miyagi Masaru
Chance Mark R
Palczewski Krzysztof
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
1878-4186
DOI
10.1016/j.str.2012.03.017
Published
2012-05-09
Pages
826-40
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC3351692
Subset
IM
Grants
NEI NIH HHS · P30 EY011373 · United States
NIGMS NIH HHS · R01 GM079191-02 · United States
NIGMS NIH HHS · GM079191 · United States
NEI NIH HHS · R01 EY008061 · United States
NIBIB NIH HHS · R01 EB009688 · United States
NIBIB NIH HHS · P30 EB009998 · United States
NIBIB NIH HHS · EB09688 · United States
NEI NIH HHS · EY008061 · United States
NEI NIH HHS · R01 EY008061-16 · United States
NEI NIH HHS · P30EY11373 · United States
NIGMS NIH HHS · R01 GM079191 · United States
NIBIB NIH HHS · P30 EB009998-03 · United States
NIBIB NIH HHS · P30EB09998 · United States
NIBIB NIH HHS · R01 EB009688-02 · United States
External Links
PubMed source DOI: 10.1016/j.str.2012.03.017 PMC Full Text View journal details
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