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Nat Commun. 2014 Sep 10;5:4801. doi: 10.1038/ncomms5801.

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

Author information

1
Institut für Medizinische Physik und Biophysik (CC2), Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
2
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.
3
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.
4
Structural Biology Group, European Synchrotron Radiation Facility, CS 40220, F-38043 Grenoble, France.
5
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.

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.

PMID:
25205354
PMCID:
PMC4199108
DOI:
10.1038/ncomms5801
[Indexed for MEDLINE]
Free PMC Article

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