Heme delivery into soluble guanylyl cyclase requires a heme redox change and is regulated by NO and Hsp90 by distinct mechanisms.

ABSTRACT: Nitric oxide (NO) signaling often relies on it activating cGMP production by the heterodimeric enzyme soluble guanylyl cyclase (sGC). To mature to function, an sGCβ subunit must first incorporate heme and then form a heterodimer with a partner α subunit. Our previous studies in cells showed that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) supplies heme to the apo-sGCβ subunit, which is complexed with the cell chaperone Hsp90. Through its ATP hydrolysis, Hsp90 then promotes heme insertion into apo-sGCβ and consequent formation of a functional heterodimer. NO at physiologic levels somehow stimulates cell heme allocation into apo-sGCβ by this process. To gain insight, we utilized purified apo-sGCβ and GAPDH reporter proteins whose heme contents can be followed by fluorescence and determi

SUBMITTER: Dai Y 

PROVIDER: S-EPMC11938259 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature