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Structural basis of arrestin-3 activation and signaling

Author

Listed:
  • Qiuyan Chen

    (Vanderbilt University)

  • Nicole A. Perry

    (Vanderbilt University)

  • Sergey A. Vishnivetskiy

    (Vanderbilt University)

  • Sandra Berndt

    (Vanderbilt University)

  • Nathaniel C. Gilbert

    (Vanderbilt University
    Louisiana State University)

  • Ya Zhuo

    (Medical College of Wisconsin)

  • Prashant K. Singh

    (Vanderbilt University)

  • Jonas Tholen

    (University of Applied Sciences Emden/Leer)

  • Melanie D. Ohi

    (Vanderbilt University
    Vanderbilt University
    Vanderbilt University)

  • Eugenia V. Gurevich

    (Vanderbilt University)

  • Chad A. Brautigam

    (The University of Texas Southwestern Medical Center)

  • Candice S. Klug

    (Medical College of Wisconsin)

  • Vsevolod V. Gurevich

    (Vanderbilt University)

  • T. M. Iverson

    (Vanderbilt University
    Vanderbilt University
    Vanderbilt University
    Vanderbilt University)

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.

Suggested Citation

  • 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 &, 2017. "Structural basis of arrestin-3 activation and signaling," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01218-8
    DOI: 10.1038/s41467-017-01218-8
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    Cited by:

    1. Pankaj Sharma & Elena Maklashina & Markus Voehler & Sona Balintova & Sarka Dvorakova & Michal Kraus & Katerina Hadrava Vanova & Zuzana Nahacka & Renata Zobalova & Stepana Boukalova & Kristyna Cunatova, 2024. "Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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