April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
The Conformation Of The Active Receptor-bound Arrestin
Author Affiliations & Notes
  • Vsevolod V. Gurevich
    Pharmacology, Vanderbilt University, Nashville, Tennessee
  • Miyeon Kim
    JSEI, UCLA, Los Angeles, California
  • Sergey A. Vishnivetskiy
    Pharmacology, Vanderbilt University, Nashville, Tennessee
  • Ned Van Eps
    JSEI, UCLA, Los Angeles, California
  • Nathan Alexander
    Pharmacology, Vanderbilt University, Nashville, Tennessee
  • Susan M. Hanson
    Pharmacology, Vanderbilt University, Nashville, Tennessee
  • Xuanzhi Zhan
    Pharmacology, Vanderbilt University, Nashville, Tennessee
  • Whitney M. Cleghorn
    Pharmacology, Vanderbilt University, Nashville, Tennessee
  • Jens Meiler
    Pharmacology, Vanderbilt University, Nashville, Tennessee
  • Wayne L. Hubbell
    JSEI, UCLA, Los Angeles, California
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 37. doi:
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      Vsevolod V. Gurevich, Miyeon Kim, Sergey A. Vishnivetskiy, Ned Van Eps, Nathan Alexander, Susan M. Hanson, Xuanzhi Zhan, Whitney M. Cleghorn, Jens Meiler, Wayne L. Hubbell; The Conformation Of The Active Receptor-bound Arrestin. Invest. Ophthalmol. Vis. Sci. 2011;52(14):37.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To determine the conformational changes in arrestin-1 upon its binding to active phosphorylated rhodopsin (P-Rh*)

Methods: : To map conformational changes upon binding to the receptor, >30 pairs of spin labels were introduced in arrestin and Double Electron-Electron Resonance (DEER) was used to monitor inter-spin distance changes.

Results: : Rod arrestin binds P-Rh* and terminates G-protein signaling. We tested a "clam shell" model, wherein the N- and C-terminal arrestin domains close upon the receptor. Based on global distance mapping, the following features were revealed: (1) the relative positions of the N- and C-domains remain largely unchanged, contrary to expectations of the clam shell model; (2) a loop implicated in the P-Rh*- arrestin interaction (the "finger loop", residues 60-80) moves toward the binding cavity of P-Rh*, but less than required to extend fully into the binding cleft on P-Rh*; (3) a striking (>10A) and unanticipated movement of a loop containing residue 139 away from the adjacent finger loop, perhaps to facilitate P-Rh* interaction with finger loop itself; (4) a loop in the C-domain containing residue 344 moves toward the receptor; (5) the C-tail is completely released. Interestingly, arrestin elements that undergo the most dramatic changes upon receptor binding described in (2) and (4) correspond to the "plastic" domains of arrestin that adopt different conformations in the monomers of the crystal structure tetramer.

Conclusions: : Concerted movement of several flexible loops mediates arrestin adjustment to the receptor. A molecular model based on this data provides the first description of the underlying conformational rearrangements and the shape of active receptor-bound arrestin.

Keywords: photoreceptors • signal transduction • protein structure/function 
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