1. Biochemistry and Chemical Biology
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Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy

  1. Benjamin G Horst
  2. Adam L Yokom
  3. Daniel J Rosenberg
  4. Kyle L Morris
  5. Michal Hammel
  6. James H Hurley  Is a corresponding author
  7. Michael A Marletta  Is a corresponding author
  1. University of California, Berkeley, United States
  2. Lawrence Berkeley National Laboratory, United States
Research Article
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Cite this article as: eLife 2019;8:e50634 doi: 10.7554/eLife.50634

Abstract

Soluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. We determined structures of full-length Manduca sexta sGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains. Repositioning of the β H-NOX domain leads to a straightening of the coiled-coil domains, which, in turn, use the motion to move the catalytic domains into an active conformation. YC-1 binds directly between the β H-NOX domain and the two CC domains. The structural elongation of the particle observed in cryo-EM was corroborated in solution using small angle X-ray scattering (SAXS). These structures delineate the endpoints of the allosteric transition responsible for the major cyclic GMP-dependent physiological effects of NO.

Article and author information

Author details

  1. Benjamin G Horst

    Department of Chemistry, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9694-7263
  2. Adam L Yokom

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3746-7961
  3. Daniel J Rosenberg

    Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8017-8156
  4. Kyle L Morris

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  5. Michal Hammel

    Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States
    Competing interests
    No competing interests declared.
  6. James H Hurley

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    jimhurley@berkeley.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5054-5445
  7. Michael A Marletta

    Department of Chemistry, University of California, Berkeley, Berkeley, United States
    For correspondence
    marletta@berkeley.edu
    Competing interests
    Michael A Marletta, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8715-4253

Funding

National Institutes of Health (GM127854)

  • Michael A Marletta

National Institutes of Health (GM066698)

  • Benjamin G Horst

National Institutes of Health (GM124169)

  • Michal Hammel

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Wilfred A van der Donk, University of Illinois at Urbana-Champaign, United States

Publication history

  1. Received: July 28, 2019
  2. Accepted: September 27, 2019
  3. Accepted Manuscript published: September 30, 2019 (version 1)
  4. Version of Record published: November 8, 2019 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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