Structure
Volume 30, Issue 2, 3 February 2022, Pages 263-277.e5
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Article
Structural evidence for visual arrestin priming via complexation of phosphoinositols

https://doi.org/10.1016/j.str.2021.10.002Get rights and content
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Highlights

  • The regulatory C-tail/N-domain interaction of arrestin-1 is resolved

  • Arrestin-1 binds InsPs using many of the same residues that hold the C-tail

  • InsP binding does not activate arrestin-1, but partially removes the C-tail

Summary

Visual arrestin (Arr1) terminates rhodopsin signaling by blocking its interaction with transducin. To do this, Arr1 translocates from the inner to the outer segment of photoreceptors upon light stimulation. Mounting evidence indicates that inositol phosphates (InsPs) affect Arr1 activity, but the Arr1-InsP molecular interaction remains poorly defined. We report the structure of bovine Arr1 in a ligand-free state featuring a near-complete model of the previously unresolved C-tail, which plays a crucial role in regulating Arr1 activity. InsPs bind to the N-domain basic patch thus displacing the C-tail, suggesting that they prime Arr1 for interaction with rhodopsin and help direct Arr1 translocation. These structures exhibit intact polar cores, suggesting that C-tail removal by InsP binding is insufficient to activate Arr1. These results show how Arr1 activity can be controlled by endogenous InsPs in molecular detail.

Keywords

arrestin
myo-D-inositol hexakisphosphate
InsP6
(1,4,5) myo-D-inositol triphosphate
InsP3
retina
phototransduction
G protein-coupled receptor
GPCR
crystal structure
phospholipase C
vision
photoreceptor

Data and code availability

  • All data reported in this paper will be shared by the lead contact upon request. This paper analyzes existing, publicly available data. The public location of the dataset is listed in the key resources table.

  • This paper does not report original code.

  • The atomic coordinates and structure factors of all structures have been deposited in the Protein Data Bank under accession codes 7F1W, 7F1X, 7JSM, 7JTB, 7JXA, 7MOR, 7MP0, 7MP1, and 7MP2. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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