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PMID: 25205354 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Crystal structure of a common GPCR-binding interface for G protein and arrestin.

Nature communications ·Vol. 5 ·2014-09-10 ·Pages 4801

Szczepek M, Beyrière F, Hofmann KP, Elgeti M, Kazmin R, Rose A, Bartl FJ, von Stetten D, Heck M, Sommer ME, Hildebrand PW, Scheerer P

Abstract

G-protein-coupled receptors (GPCRs) transmit extracellular signals to activate intracellular heterotrimeric G proteins (Gαβγ) and arrestins. For G protein signalling, the Gα C-terminus (GαCT) binds to a cytoplasmic crevice of the receptor that opens upon activation. A consensus motif is shared among GαCT from the Gi/Gt family and the 'finger loop' region (ArrFL1-4) of all four arrestins. Here we present a 2.75 Å crystal structure of ArrFL-1, a peptide analogue of the finger loop of rod photoreceptor arrestin, in complex with the prototypical GPCR rhodopsin. Functional binding of ArrFL to the receptor was confirmed by ultraviolet-visible absorption spectroscopy, competitive binding assays and Fourier transform infrared spectroscopy. For both GαCT and ArrFL, binding to the receptor crevice induces a similar reverse turn structure, although significant structural differences are seen at the rim of the binding crevice. Our results reflect both the common receptor-binding interface and the divergent biological functions of G proteins and arrestins.

MeSH Terms
Amino Acid Motifs Animals Arrestins/metabolism Binding, Competitive Cattle Crystallography, X-Ray Models, Molecular Protein Structure, Tertiary Receptors, G-Protein-Coupled/metabolism Rhodopsin/metabolism Signal Transduction Spectroscopy, Fourier Transform Infrared X-Ray Absorption Spectroscopy
Chemicals
Arrestins Receptors, G-Protein-Coupled Rhodopsin
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Szczepek Michal
Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Beyrière Florent
Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Hofmann Klaus Peter
1] Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany [2] Zentrum für Biophysik und Bioinformatik, Humboldt-Universität zu Berlin, Invalidenstrasse 42, D-10115 Berlin, Germany.
Elgeti Matthias
Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Kazmin Roman
Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Rose Alexander
1] Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany [2] Institut für Medizinische Physik und Biophysik (CC2), AG ProteiInformatics, Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Bartl Franz J
1] Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany [2] Zentrum für Biophysik und Bioinformatik, Humboldt-Universität zu Berlin, Invalidenstrasse 42, D-10115 Berlin, Germany.
von Stetten David
Structural Biology Group, European Synchrotron Radiation Facility, CS 40220, F-38043 Grenoble, France.
Heck Martin
Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Sommer Martha E
Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Hildebrand Peter W
1] Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany [2] Institut für Medizinische Physik und Biophysik (CC2), AG ProteiInformatics, Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Scheerer Patrick
1] Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany [2] Institut für Medizinische Physik und Biophysik (CC2), AG Protein X-ray Crystallography, Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms5801
Published
2014-09-10
Epub
2014-00-10
Pages
4801
Language
English
Region
England
NLM ID
101528555
PMCID
PMC4199108
Subset
IM
Databases
PDB
4PXF
External Links
PubMed source DOI: 10.1038/ncomms5801 PMC Full Text View journal details
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