title: ATP bimodal switch that regulates the ligand binding and signal transduction activities of the atrial natriuretic factor receptor guanylate cyclase.
abstract: Atrial natriuretic factor (ANF)-dependent guanylate cyclase (ANF-RGC) is a single-chain transmembrane-spanning protein, containing both ANF binding and catalytic cyclase activity. ANF binding to the extracellular receptor domain activates the cytosolic catalytic domain, generating the second messenger cyclic GMP. Obligatory in this activation process is an intervening step regulated by the ATP binding to the cyclase. This is a signal transduction step that bridges the events of ligand binding and cyclase activation. A defined structural motif (Gly503-Xa-Gly505-Xa-Xa-Xa-Gly509), termed ATP regulatory module (ARM), is critical for this step. The present study shows that the ARM-Gly505 residue acts as an ATP bimodal switch in regulating both the ligand binding and signal transduction activities of ANF-RGC, thus representing a critical site to turn the hormone signal on and off.
authors.affiliation: Unit of Regulatory and Molecular Biology, Pennsylvania College of Optometry, Philadelphia 19141, USA.
authors.forename: T
authors.initials: T
authors.lastname: Duda
authors.forename: R K
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002522:Chlorocebus aethiops; D006162:Guanylate Cyclase / Q000378:metabolism*; D008024:Ligands; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor