| First Author | Vishnivetskiy SA | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 17 | Pages | 11741-50 |
| PubMed ID | 23476014 | Mgi Jnum | J:198602 |
| Mgi Id | MGI:5498444 | Doi | 10.1074/jbc.M113.450031 |
| Citation | Vishnivetskiy SA, et al. (2013) Critical role of the central 139-loop in stability and binding selectivity of arrestin-1. J Biol Chem 288(17):11741-50 |
| abstractText | Arrestin-1 selectively binds active phosphorylated rhodopsin (P-Rh*), demonstrating much lower affinity for inactive phosphorylated (P-Rh) and unphosphorylated active (Rh*) forms. Receptor interaction induces significant conformational changes in arrestin-1, which include large movement of the previously neglected 139-loop in the center of the receptor binding surface, away from the incoming receptor. To elucidate the functional role of this loop, in mouse arrestin-1 we introduced deletions of variable lengths and made several substitutions of Lys-142 in it and Asp-72 in the adjacent loop. Several mutants with perturbations in the 139-loop demonstrate increased binding to P-Rh*, dark P-Rh, Rh*, and phospho-opsin. Enhanced binding of arrestin-1 mutants to non-preferred forms of rhodopsin correlates with decreased thermal stability. The 139-loop perturbations increase P-Rh* binding of arrestin-1 at low temperatures and further change its binding profile on the background of 3A mutant, where the C-tail is detached from the body of the molecule by triple alanine substitution. Thus, the 139-loop stabilizes basal conformation of arrestin-1 and acts as a brake, preventing its binding to non-preferred forms of rhodopsin. Conservation of this loop in other subtypes suggests that it has the same function in all members of the arrestin family. |
