PMID- 31566566
OWN - NLM
STAT- MEDLINE
DCOM- 20200312
LR  - 20211208
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 8
DP  - 2019 Sep 30
TI  - Allosteric activation of the nitric oxide receptor soluble guanylate cyclase 
      mapped by cryo-electron microscopy.
LID - 10.7554/eLife.50634 [doi]
LID - e50634
AB  - 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 degrees  rotation of the heme-binding beta 
      H-NOX and PAS domains. Repositioning of the beta 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 beta 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.
FAU - Horst, Benjamin G
AU  - Horst BG
AUID- ORCID: 0000-0001-9694-7263
AD  - Department of Chemistry, University of California, Berkeley, Berkeley, United 
      States.
FAU - Yokom, Adam L
AU  - Yokom AL
AUID- ORCID: 0000-0002-3746-7961
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, 
      Berkeley, United States.
AD  - Graduate Group in Biophysics, University of California, Berkeley, Berkeley, 
      United States.
FAU - Rosenberg, Daniel J
AU  - Rosenberg DJ
AUID- ORCID: 0000-0001-8017-8156
AD  - Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National 
      Laboratory, Berkeley, United States.
AD  - California Institute for Quantitative Biosciences, University of California, 
      Berkeley, Berkeley, United States.
FAU - Morris, Kyle L
AU  - Morris KL
AUID- ORCID: 0000-0002-1717-8134
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, 
      Berkeley, United States.
AD  - Graduate Group in Biophysics, University of California, Berkeley, Berkeley, 
      United States.
FAU - Hammel, Michal
AU  - Hammel M
AD  - Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National 
      Laboratory, Berkeley, United States.
FAU - Hurley, James H
AU  - Hurley JH
AUID- ORCID: 0000-0001-5054-5445
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, 
      Berkeley, United States.
AD  - Graduate Group in Biophysics, University of California, Berkeley, Berkeley, 
      United States.
AD  - Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National 
      Laboratory, Berkeley, United States.
AD  - California Institute for Quantitative Biosciences, University of California, 
      Berkeley, Berkeley, United States.
FAU - Marletta, Michael A
AU  - Marletta MA
AUID- ORCID: 0000-0001-8715-4253
AD  - Department of Chemistry, University of California, Berkeley, Berkeley, United 
      States.
AD  - Department of Molecular and Cell Biology, University of California, Berkeley, 
      Berkeley, United States.
AD  - Graduate Group in Biophysics, University of California, Berkeley, Berkeley, 
      United States.
LA  - eng
SI  - PDB/6PAS
SI  - PDB/6PAT
GR  - GM066698/NH/NIH HHS/United States
GR  - GM127854/NH/NIH HHS/United States
GR  - S10OD018483/NH/NIH HHS/United States
GR  - P30 GM124169/GM/NIGMS NIH HHS/United States
GR  - GM124169/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190930
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Indazoles)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 4.6.1.2 (Soluble Guanylyl Cyclase)
SB  - IM
CIN - Elife. 2019 Nov 08;8:. PMID: 31701871
MH  - Allosteric Regulation
MH  - Animals
MH  - *Cryoelectron Microscopy
MH  - Indazoles/metabolism
MH  - Manduca/*enzymology
MH  - Nitric Oxide/metabolism
MH  - Protein Conformation
MH  - Soluble Guanylyl Cyclase/*ultrastructure
PMC - PMC6839917
OTO - NOTNLM
OT  - CryoEM
OT  - SAXS
OT  - allostery
OT  - biochemistry
OT  - chemical biology
OT  - cyclic GMP
OT  - manduca sexta
OT  - nitric oxide
OT  - none
COIS- BH, AY, DR, KM, MH, JH No competing interests declared, MM Reviewing editor, 
      eLife
EDAT- 2019/10/01 06:00
MHDA- 2020/03/13 06:00
PMCR- 2019/09/30
CRDT- 2019/10/01 06:00
PHST- 2019/07/28 00:00 [received]
PHST- 2019/09/27 00:00 [accepted]
PHST- 2019/10/01 06:00 [pubmed]
PHST- 2020/03/13 06:00 [medline]
PHST- 2019/10/01 06:00 [entrez]
PHST- 2019/09/30 00:00 [pmc-release]
AID - 50634 [pii]
AID - 10.7554/eLife.50634 [doi]
PST - epublish
SO  - Elife. 2019 Sep 30;8:e50634. doi: 10.7554/eLife.50634.