Structural basis of arrestin-3 activation and signaling

Journal Article · Fri Nov 10 04:00:00 EST 2017 · Nature Communications

DOI:https://doi.org/10.1038/s41467-017-01218-8· OSTI ID:1410119

Chen, Qiuyan; Perry, Nicole A.; Vishnivetskiy, Sergey A.; Berndt, Sandra; Gilbert, Nathaniel C.; Zhuo, Ya; Singh, Prashant K.; Tholen, Jonas; Ohi, Melanie D.; Gurevich, Eugenia V.; Brautigam, Chad A.; Klug, Candice S.; Gurevich, Vsevolod V.; Iverson, T. M.

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 promote arrestin-3 activation by IP6. Importantly, we show that effector-binding sites on arrestins have distinct conformations in the basal and activated states, acting as switch regions. These switch regions may work with the inter-domain twist to initiate and direct arrestin-mediated signaling.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: UNIVERSITYNIH
• OSTI ID: 1410119
• Journal Information: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 8; ISSN 2041-1723
• Publisher: Nature Publishing Group
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES