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A model for the solution structure of the rod arrestin tetramer. Structure 2008 Jun;16(6):924-34

Date

06/13/2008

Pubmed ID

18547524

Pubmed Central ID

PMC2464289

DOI

10.1016/j.str.2008.03.006

Scopus ID

2-s2.0-44649193852 (requires institutional sign-in at Scopus site)   67 Citations

Abstract

Visual rod arrestin has the ability to self-associate at physiological concentrations. We previously demonstrated that only monomeric arrestin can bind the receptor and that the arrestin tetramer in solution differs from that in the crystal. We employed the Rosetta docking software to generate molecular models of the physiologically relevant solution tetramer based on the monomeric arrestin crystal structure. The resulting models were filtered using the Rosetta energy function, experimental intersubunit distances measured with DEER spectroscopy, and intersubunit contact sites identified by mutagenesis and site-directed spin labeling. This resulted in a unique model for subsequent evaluation. The validity of the model is strongly supported by model-directed crosslinking and targeted mutagenesis that yields arrestin variants deficient in self-association. The structure of the solution tetramer explains its inability to bind rhodopsin and paves the way for experimental studies of the physiological role of rod arrestin self-association.

Author List

Hanson SM, Dawson ES, Francis DJ, Van Eps N, Klug CS, Hubbell WL, Meiler J, Gurevich VV

Author

Candice S. Klug PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Arrestin
Disulfides
Electron Spin Resonance Spectroscopy
Models, Molecular
Protein Conformation
Protein Subunits
Sequence Deletion
Software
Solutions
Spin Labels