5TV1

active arrestin-3 with inositol hexakisphosphate

Summary for 5TV1

• Entry DOI: 10.2210/pdb5tv1/pdb
• Descriptor: Beta-arrestin-2, INOSITOL HEXAKISPHOSPHATE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: signaling protein
• Biological source: Bos taurus (Bovine)
• Total number of polymer chains: 1
• Total formula weight: 45859.88

Authors

Chen, Q.,Gilbert, N.C.,Perry, N.A.,Vishniveteskiy, S.,Gurevich, V.V.,Iverson, T.M. (deposition date: 2016-11-07, release date: 2017-11-22, Last modification date: 2023-10-04)

Primary citation

Chen, Q.,Perry, N.A.,Vishnivetskiy, S.A.,Berndt, S.,Gilbert, N.C.,Zhuo, Y.,Singh, P.K.,Tholen, J.,Ohi, M.D.,Gurevich, E.V.,Brautigam, C.A.,Klug, C.S.,Gurevich, V.V.,Iverson, T.M.
Structural basis of arrestin-3 activation and signaling.
Nat Commun, 8:1427-1427, 2017

PubMed 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 (IP) is a non-receptor activator of arrestin-3 and report the structure of IP-activated arrestin-3 at 2.4-Å resolution. IP-activated arrestin-3 exhibits an inter-domain twist and a displaced C-tail, hallmarks of active arrestin. IP 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 IP. 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.

PubMed: 29127291
DOI: 10.1038/s41467-017-01218-8

Experimental method

X-RAY DIFFRACTION (2.4 Å)