Cholesterol Derivatives Regulate Adenylyl Cyclase 7 Activity by Binding CARC and CRAC Motifs in the Cytosolic Subunits.

ABSTRACT: Transmembrane adenylyl cyclases (tmACs; ACs) are enzymes that synthesize cyclic AMP (cAMP), which is a key molecule in cellular signaling. Disruptions in AC activity can lead to long-term shifts in cAMP levels associated with various pathologies. In our study, we analyzed AC primary sequences and identified cholesterol-binding CARC and CRAC motifs located in conserved cytosolic regions, a surprising finding for motifs that are typically membrane-associated. Focusing on AC7, we mapped these motifs within its predicted structure and performed docking studies with cholesterol derivatives (hydrocortisone, dexamethasone, and 25-hydroxycholesterol). Our results showed that these molecules predominantly bind to the forskolin (FSK) binding site, which contains two CARC motifs. Using membranes over

SUBMITTER: Jarousek R 

PROVIDER: S-EPMC12391971 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature