Structural basis of arrestin-3 activation and signaling.

ABSTRACT: A unique aspect of arrestin-3 is its ability to support both receptor-dependent and receptor-independent signaling. Here, we show that inositol hexakisphosphate (IP₆) is a non-receptor activator of arrestin-3 and report the structure of IP₆-activated arrestin-3 at 2.4-Å resolution. IP₆-activated arrestin-3 exhibits an inter-domain twist and a displaced C-tail, hallmarks of active arrestin. IP₆ binds to the arrestin phosphate sensor, and is stabilized by trimerization. Analysis of the trimerization surface, which is also the receptor-binding surface, suggests a feature called the finger loop as a key region of the activation sensor. We show that finger loop helicity and flexibility may underlie coupling to hundreds of diverse receptors and also pr

SUBMITTER: Chen Q 

PROVIDER: S-EPMC5681653 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature