cGMP controls many cellular functions ranging from growth, viability, and differentiation to contractility, secretion, and ion transport. The mammalian genome encodes seven transmembrane guanylyl cyclases (GCs), GC-A to GC-G, which mainly modulate submembrane cGMP microdomains. These GCs share a unique topology comprising an extracellular domain, a short transmembrane region, and an intracellul...

Cyclic GMP (cGMP) is an important second messenger in eukaryotes. It is formed by guanylyl cyclases (GCs), members of the nucleotidyl cyclases class III, which also comprises adenylyl cyclases (ACs) from most organisms. To date, no structures of eukaryotic GCs are available, and all bacterial class III proteins were found to be ACs. Here we describe the biochemical and structural characterizati...

Conventional soluble guanylyl cyclases form alpha/beta heterodimers that are activated by nitric oxide (NO). Recently, atypical members of the soluble guanylyl cyclase family have been described that include the rat beta2 subunit and MsGC-beta3 from Manduca sexta. Predictions from the Drosophila melanogaster genome identify three atypical guanylyl cyclase subunits: Gyc-88E (formerly CG4154), Gy...

Soluble guanylyl cyclases are typically obligate heterodimers, composed of a single alpha and a single beta subunit. MsGC-beta3, identified in the tobacco hornworm Manduca sexta, was the first example of a soluble guanylyl cyclase that exhibited enzyme activity without the need for coexpression with additional subunits. Subsequent studies have revealed that the mammalian beta2 subunit also shar...