Article
Single-particle EM reveals the higher-order domain architecture of soluble guanylate cyclase
Proceedings of the National Academy of Sciences
(2014)
Abstract
Soluble guanylate cyclase (sGC) is the primary nitric oxide (NO) receptor in mammals and a central component of the NO-signaling pathway. The NO-signaling pathways mediate diverse physiological processes, including vasodilation, neurotransmission, and myocardial functions. sGC is a heterodimer assembled from two homologous subunits, each comprised of four domains. Although crystal structures of isolated domains have been reported, no structure is available for full-length sGC. We used single-particle electron microscopy to obtain the structure of the complete sGC heterodimer and determine its higher-order domain architecture. Overall, the protein is formed of two rigid modules: the catalytic dimer and the clustered Per/Art/Sim and heme-NO/O2-binding domains, connected by a parallel coiled coil at two hinge points. The quaternary assembly demonstrates a very high degree of flexibility. We captured hundreds of individual conformational snapshots of free sGC, NO-bound sGC, and guanosine-5′-[(α,β)-methylene]triphosphate-bound sGC. The molecular architecture and pronounced flexibility observed provides a significant step forward in understanding the mechanism of NO signaling.
Disciplines
Publication Date
2014
DOI
10.1073/pnas.1400711111
Publisher Statement
Copyright 2014 National Academy of Sciences
Citation Information
Melody G. Campbell, Eric S. Underbakke, Clinton S. Potter, Bridget Carragher, et al.. "Single-particle EM reveals the higher-order domain architecture of soluble guanylate cyclase" Proceedings of the National Academy of Sciences Vol. 111 Iss. 8 (2014) p. 2960 - 2965 Available at: http://works.bepress.com/eric-underbakke/1/