Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy
- University of California, Berkeley, United States
- Lawrence Berkeley National Laboratory, United States
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.
Data availability
Maps have been deposited to EMDB (20282, 20283) as well the C-alpha traces are deposited to the PDB (6PAS, 6PAT) for the inactive and active states.
Article and author information
Author details
Daniel J Rosenberg
Michael A Marletta
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.
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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Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy
eLife 8:e50634.
https://doi.org/10.7554/eLife.50634
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