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Structure. 2001 Sep;9(9):869-80.

Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane Translocation.

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. mhan@mpi.com

Abstract

BACKGROUND:

Arrestins are responsible for the desensitization of many sequence-divergent G protein-coupled receptors. They compete with G proteins for binding to activated phosphorylated receptors, initiate receptor internalization, and activate additional signaling pathways.

RESULTS:

In order to understand the structural basis for receptor binding and arrestin's function as an adaptor molecule, we determined the X-ray crystal structure of two truncated forms of bovine beta-arrestin in its cytosolic inactive state to 1.9 A. Mutational analysis and chimera studies identify the regions in beta-arrestin responsible for receptor binding specificity. beta-arrestin demonstrates high structural homology with the previously solved visual arrestin. All key structural elements responsible for arrestin's mechanism of activation are conserved.

CONCLUSIONS:

Based on structural analysis and mutagenesis data, we propose a previously unappreciated part in beta-arrestin's mode of action by which a cationic amphipathic helix may function as a reversible membrane anchor. This novel activation mechanism would facilitate the formation of a high-affinity complex between beta-arrestin and an activated receptor regardless of its specific subtype. Like the interaction between beta-arrestin's polar core and the phosphorylated receptor, such a general activation mechanism would contribute to beta-arrestin's versatility as a regulator of many receptors.

PMID:
11566136
DOI:
10.1016/s0969-2126(01)00644-x
[Indexed for MEDLINE]
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