Structural insights into the mechanism of human soluble guanylate cyclase

Soluble guanylate cyclase (sGC) is the primary sensor of nitric oxide. It has a central role in nitric oxide signalling and has been implicated in many essential physiological processes and disease conditions. The binding of nitric oxide boosts the enzymatic activity of sGC. However, the mechanism b...

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Vydáno v:	Nature (London) Ročník 574; číslo 7777; s. 206 - 210
Hlavní autoři:	Kang, Yunlu, Liu, Rui, Wu, Jing-Xiang, Chen, Lei
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.10.2019 Nature Publishing Group
Témata:	101/28 631/443/1338/1872 631/45/607 631/535/1258/1259 631/80/86 692/699/75 82/16 82/29 82/80 82/83 Angina pectoris Animals Binding Catalysis Cryoelectron Microscopy Disease Disulfides - chemistry Disulfides - metabolism Domains Drosophila melanogaster Electron microscopy Enzymatic activity Enzyme Activation Guanylate cyclase Health aspects HEK293 Cells Heme - metabolism Humanities and Social Sciences Humans Hydrazines - pharmacology Kinases Mice Microscopy Models, Molecular Modules multidisciplinary Nitric oxide Nitric Oxide - metabolism Nitric Oxide Donors - metabolism Oxygen Oxygen - metabolism Physiological aspects Physiology Protein Domains Protein Multimerization Protein research Proteins Science Science (multidisciplinary) Sensors Soluble Guanylyl Cyclase - chemistry Soluble Guanylyl Cyclase - genetics Soluble Guanylyl Cyclase - metabolism Soluble Guanylyl Cyclase - ultrastructure Structure China
ISSN:	0028-0836, 1476-4687, 1476-4687
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Shrnutí:	Soluble guanylate cyclase (sGC) is the primary sensor of nitric oxide. It has a central role in nitric oxide signalling and has been implicated in many essential physiological processes and disease conditions. The binding of nitric oxide boosts the enzymatic activity of sGC. However, the mechanism by which nitric oxide activates the enzyme is unclear. Here we report the cryo-electron microscopy structures of the human sGCα1β1 heterodimer in different functional states. These structures revealed that the transducer module bridges the nitric oxide sensor module and the catalytic module. Binding of nitric oxide to the β1 haem-nitric oxide and oxygen binding (H-NOX) domain triggers the structural rearrangement of the sensor module and a conformational switch of the transducer module from bending to straightening. The resulting movement of the N termini of the catalytic domains drives structural changes within the catalytic module, which in turn boost the enzymatic activity of sGC. Cryo-electron microscopy structures of human soluble guanylate cyclase in inactive and activated states shed light on the activation mechanism of this enzyme by nitric oxide.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-019-1584-6