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Surveying non-visual arrestins reveals allosteric interactions between functional sites
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  • James M. Seckler,
  • Emily N. Robinson,
  • Stephen J. Lewis,
  • Alan Grossfield
James M. Seckler
Case Western Reserve University Department of Biomedical Engineering

Corresponding Author:[email protected]

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Emily N. Robinson
University of Rochester
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Stephen J. Lewis
Case Western Reserve University
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Alan Grossfield
University of Rochester
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Arrestins are important scaffolding proteins that are expressed in all vertebrate animals. They regulate cell signaling events upon binding to active G-protein coupled receptors ( GPCR) and trigger endocytosis of active GPCRs. While many of the functional sites on arrestins have been characterized, the question of how these sites interact is unanswered. We used anisotropic network modelling ( ANM) together with our covariance compliment techniques to survey all of the available structures of the non-visual arrestins to map how structural changes and protein-binding affect their structural dynamics. We found that activation and clathrin binding have a marked effect on arrestin dynamics, and that these dynamics changes are localized to a small number of distant functional sites. These sites include α-helix 1, the lariat loop, nuclear localization domain, and the C-domain β-sheets on the C-loop side. Our techniques suggest that clathrin binding and/or GPCR activation of arrestin perturb the dynamics of these sites independent of structural changes.
23 May 2022Submitted to PROTEINS: Structure, Function, and Bioinformatics
23 May 2022Submission Checks Completed
23 May 2022Assigned to Editor
28 May 2022Reviewer(s) Assigned
26 Jun 2022Review(s) Completed, Editorial Evaluation Pending
27 Jun 2022Editorial Decision: Revise Major
26 Jul 20221st Revision Received
26 Jul 2022Submission Checks Completed
26 Jul 2022Assigned to Editor
26 Jul 2022Reviewer(s) Assigned
11 Aug 2022Review(s) Completed, Editorial Evaluation Pending
11 Aug 2022Editorial Decision: Accept
21 Aug 2022Published in Proteins: Structure, Function, and Bioinformatics. 10.1002/prot.26413