sGCα1/sGCβ1 GST Tag Protein, Human

sGCα1/β1 (Soluble Guanylate Cyclase α1/β1 Heterodimer), encoded by the GUCY1A1 and GUCY1B1 genes, is a heterodimeric heme-containing metalloprotein belonging to the soluble guanylate cyclase family. The GUCY1A1–GUCY1B1 heterodimer is the predominant and functionally dominant isoform of sGC in most tissues. It serves as the primary intracellular receptor for nitric oxide (NO), the endothelium-derived gasotransmitter central to cardiovascular homeostasis. The sGCα1/β1 complex does not exist as a functional NO sensor in the absence of its heme prosthetic group. Maturation requires the chaperone Hsp90, which associates with the heme-free (apo) β1 subunit and drives ferrous heme insertion; this event triggers Hsp90 dissociation and permits β1 to bind α1, yielding the mature, NO-responsive heterodimer. NO binds to the ferrous heme within the β1 subunit’s H-NOX domain, breaking the axial Fe–His105 bond and initiating a “closed-to-open” transition in the heme pocket. This local change propagates through the PAS and coiled-coil domains, straightening the coiled-coil helices and driving the catalytic domain into a closed, active conformation. Activated sGCα1/β1 catalyzes the conversion of GTP to the second messenger cGMP, which in turn activates cGMP-dependent protein kinase (PKG); PKG phosphorylates downstream substrates and also feeds back to phosphorylate sGCα1 at Ser64, establishing a negative feedback loop. The α1β1 heterodimer is highly expressed in the cardiovascular system, platelets, and brain, where it mediates vasodilation, inhibition of platelet aggregation, and neuronal signaling. Disruption of sGCα1/β1 function is pathophysiologically linked to hypertension—male sGCα1-knockout mice develop spontaneous hypertension—and to pulmonary arterial hypertension, in which reduced sGC expression and impaired α1β1 heterodimer formation contribute to NO–sGC–cGMP signaling dysfunction.