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PMID: 28220785 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

C-edge loops of arrestin function as a membrane anchor.

Nature communications ·Vol. 8 ·2017-00-21 ·Pages 14258

Lally CC, Bauer B, Selent J, Sommer ME

Abstract

G-protein-coupled receptors are membrane proteins that are regulated by a small family of arrestin proteins. During formation of the arrestin-receptor complex, arrestin first interacts with the phosphorylated receptor C terminus in a pre-complex, which activates arrestin for tight receptor binding. Currently, little is known about the structure of the pre-complex and its transition to a high-affinity complex. Here we present molecular dynamics simulations and site-directed fluorescence experiments on arrestin-1 interactions with rhodopsin, showing that loops within the C-edge of arrestin function as a membrane anchor. Activation of arrestin by receptor-attached phosphates is necessary for C-edge engagement of the membrane, and we show that these interactions are distinct in the pre-complex and high-affinity complex in regard to their conformation and orientation. Our results expand current knowledge of C-edge structure and further illuminate the conformational transitions that occur in arrestin along the pathway to tight receptor binding.

MeSH Terms
Amino Acid Sequence Animals Arrestins/chemistry,genetics,metabolism Base Sequence Binding Sites/genetics Cattle Cell Membrane/metabolism Molecular Dynamics Simulation Multiprotein Complexes/chemistry,metabolism Mutation Phosphorylation Protein Binding Protein Conformation Rhodopsin/chemistry,metabolism
Chemicals
Arrestins Multiprotein Complexes arrestin 1 protein, mouse Rhodopsin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lally Ciara C M
Institute of Medical Physics and Biophysics (CC2), Charité Medical University, Charitéplatz 1, Berlin 10117, Germany.
Bauer Brian
Institute of Medical Physics and Biophysics (CC2), Charité Medical University, Charitéplatz 1, Berlin 10117, Germany.
Selent Jana
Research Programme on Biomedical Informatics, Department of Experimental and Health Sciences, Pompeu Fabra University, Hospital del Mar Medical Research Institute, Carrer del Dr. Aiguader, 88, Barcelona 08003, Spain.
Sommer Martha E
Institute of Medical Physics and Biophysics (CC2), Charité Medical University, Charitéplatz 1, Berlin 10117, Germany.
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms14258
Published
2017-00-21
Epub
2017-00-21
Pages
14258
Language
English
Region
England
NLM ID
101528555
PMCID
PMC5321764
Subset
IM
External Links
PubMed source DOI: 10.1038/ncomms14258 PMC Full Text View journal details
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