Architecture and activation of single-pass transmembrane receptor guanylyl cyclase. Nat Struct Mol Biol 2025 Mar;32(3):469-478
Date
11/15/2024Pubmed ID
39543315Pubmed Central ID
PMC12493526DOI
10.1038/s41594-024-01426-zScopus ID
2-s2.0-85208990896 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
The heart, in addition to its primary role in blood circulation, functions as an endocrine organ by producing cardiac hormone natriuretic peptides. These hormones regulate blood pressure through the single-pass transmembrane receptor guanylyl cyclase A (GC-A), also known as natriuretic peptide receptor 1. The binding of the peptide hormones to the extracellular domain of the receptor activates the intracellular guanylyl cyclase domain of the receptor to produce the second messenger cyclic guanosine monophosphate. Despite their importance, the detailed architecture and domain interactions within full-length GC-A remain elusive. Here we present cryo-electron microscopy structures, functional analyses and molecular dynamics simulations of full-length human GC-A, in both the absence and the presence of atrial natriuretic peptide. The data reveal the architecture of full-length GC-A, highlighting the spatial arrangement of its various functional domains. This insight is crucial for understanding how different parts of the receptor interact and coordinate during activation. The study elucidates the molecular basis of how extracellular signals are transduced across the membrane to activate the intracellular guanylyl cyclase domain.
Author List
Liu S, Payne AM, Wang J, Zhu L, Paknejad N, Eng ET, Liu W, Miao Y, Hite RK, Huang XYAuthors
Wei Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinLan Zhu PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Atrial Natriuretic FactorCryoelectron Microscopy
Guanylate Cyclase
Humans
Models, Molecular
Molecular Dynamics Simulation
Protein Binding
Protein Domains
Receptors, Atrial Natriuretic Factor
