Structural basis of arrestin-3 activation and signaling

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 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.

Original languageEnglish (US)
Article number1427
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Arrestin
Chemical activation
activation
switches
Fingers
inositols
effectors
Arrestins
sensors
Phytic Acid
phosphates
flexibility
Switches
Phosphates
Binding Sites
beta-Arrestin 2
Sensors
Conformations

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Chen, Q., Perry, N. A., Vishnivetskiy, S. A., Berndt, S., Gilbert, N. C., Zhuo, Y., ... Iverson, T. M. (2017). Structural basis of arrestin-3 activation and signaling. Nature Communications, 8(1), [1427]. https://doi.org/10.1038/s41467-017-01218-8

Structural basis of arrestin-3 activation and signaling. / 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.

In: Nature Communications, Vol. 8, No. 1, 1427, 01.12.2017.

Research output: Contribution to journalArticle

Chen, Q, Perry, NA, Vishnivetskiy, SA, Berndt, S, Gilbert, NC, Zhuo, Y, Singh, PK, Tholen, J, Ohi, MD, Gurevich, EV, Brautigam, CA, Klug, CS, Gurevich, VV & Iverson, TM 2017, 'Structural basis of arrestin-3 activation and signaling', Nature Communications, vol. 8, no. 1, 1427. https://doi.org/10.1038/s41467-017-01218-8
Chen Q, Perry NA, Vishnivetskiy SA, Berndt S, Gilbert NC, Zhuo Y et al. Structural basis of arrestin-3 activation and signaling. Nature Communications. 2017 Dec 1;8(1). 1427. https://doi.org/10.1038/s41467-017-01218-8
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. / Structural basis of arrestin-3 activation and signaling. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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