6JT2

Structure of human soluble guanylate cyclase in the NO activated state

Summary for 6JT2

• Entry DOI: 10.2210/pdb6jt2/pdb
• EMDB information: 9885
• Descriptor: Guanylate cyclase soluble subunit alpha-1, Guanylate cyclase soluble subunit beta-1, PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER, ... (5 entities in total)
• Functional Keywords: soluble guanylate cyclase, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 149352.11

Authors

Chen, L.,Kang, Y.,Liu, R.,Wu, J.-X. (deposition date: 2019-04-08, release date: 2019-09-04, Last modification date: 2024-03-27)

Primary citation

Kang, Y.,Liu, R.,Wu, J.X.,Chen, L.
Structural insights into the mechanism of human soluble guanylate cyclase.
Nature, 574:206-210, 2019

PubMed Abstract: 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.

PubMed: 31514202
DOI: 10.1038/s41586-019-1584-6

Experimental method

ELECTRON MICROSCOPY (3.8 Å)