Format

Send to

Choose Destination
Elife. 2019 Sep 30;8. pii: e50634. doi: 10.7554/eLife.50634.

Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy.

Author information

1
Department of Chemistry, University of California, Berkeley, Berkeley, United States.
2
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.
3
Graduate Group in Biophysics, University of California, Berkeley, Berkeley, United States.
4
Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, United States.
5
California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States.
#
Contributed equally

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.

KEYWORDS:

CryoEM; SAXS; allostery; biochemistry; chemical biology; cyclic GMP; manduca sexta; nitric oxide; none

PMID:
31566566
DOI:
10.7554/eLife.50634
Free full text

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd
Loading ...
Support Center