The selectivity of visual arrestin for light-activated phosphorhodopsin is controlled by multiple nonredundant mechanisms.

Gurevich VV
J Biol Chem. 1998 273 (25): 15501-6

PMID: 9624137 · DOI:10.1074/jbc.273.25.15501

Arrestin plays an important role in quenching phototransduction via its ability to bind to the phosphorylated light-activated form of the visual receptor rhodopsin (P-Rh*). Remarkable selectivity of visual arrestin toward this functional form is determined by an elegant sequential multisite binding mechanism. Previous structure-function studies have suggested that the COOH-terminal region of arrestin (residues 356-404) is not directly involved in rhodopsin interaction, but instead plays a regulatory role. This region supports basal arrestin conformation and ensures arrestin's transition into a high affinity rhodopsin-binding state upon an encounter with P-Rh*. Overall, our results corroborate this hypothesis and identify three functional subregions (residues 361-368, 369-378, and 379-404) and individual amino acids involved in the control of arrestin stability and binding selectivity. Two of the most potent mutants, arrestin(1-378) and arrestin(F375A,V376A, F377A) belong to a novel class of constitutively active arrestins with high affinity for P-Rh*, dark P-Rh, and Rh* (but not dark Rh), in contrast to earlier constructed mutants arrestin(R175E) and arrestin(Delta2-16) with high affinity for light-activated forms only. The implications of these findings for the mechanism of arrestin-rhodopsin interaction are discussed in light of the recently determined crystal structure of arrestin.

MeSH Terms (17)

Amino Acid Sequence Animals Arrestin Binding Sites Cattle Crystallography, X-Ray Eye Proteins G-Protein-Coupled Receptor Kinase 1 Humans Light Molecular Sequence Data Phosphorylation Protein Conformation Protein Kinases Rhodopsin Sequence Alignment Structure-Activity Relationship

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