Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Graduate Group in Biophysics, University of California, Berkeley, Berkeley, United States
Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, United States; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Graduate Group in Biophysics, University of California, Berkeley, Berkeley, United States
Michal Hammel
Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, United States
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Graduate Group in Biophysics, University of California, Berkeley, Berkeley, United States; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, United States; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States
Department of Chemistry, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Graduate Group in Biophysics, University of California, Berkeley, Berkeley, United States
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.
