Journal Article PUBDB-2015-04295

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Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

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2015
Macmillan28177 London

Nature 523(7562), 561 - 567 () [10.1038/nature14656]
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Abstract: G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin–arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ~20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.

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Note: (c) Macmillan Publishers Limited. Post referee full text in progress. Embargo for post referee full text 6 months from 22 July 2015.

Contributing Institute(s):
  1. CFEL-Coherent X-Ray Imaging (FS-CFEL-1)
Research Program(s):
  1. 6215 - Soft Matter, Health and Life Sciences (POF3-621) (POF3-621)
Experiment(s):
  1. Experiments at CFEL
  2. Measurement at external facility

Appears in the scientific report 2015
Database coverage:
Medline ; NCBI Molecular Biology Database ; SCOPUS
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 Record created 2015-10-21, last modified 2025-07-17


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