title: Allosteric regulatory step and configuration of the ATP-binding pocket in atrial natriuretic factor receptor guanylate cyclase transduction mechanism.
abstract: The atrial natriuretic factor (ANF) signal transduction mechanism consists of the transformation of the signal information into the production of cyclic GMP. The binding of ANF to its receptor, which is also a guanylate cyclase, generates the signal. This cyclase has been termed atrial natriuretic factor receptor guanylate cyclase, ANF-RGC. ANF-RGC is a single transmembrane-spanning protein. The ANF receptor domain resides in the extracellular region of the protein, and the catalytic domain is located in the intracellular region at the C-terminus of the protein. Thus, the signal is relayed progressively from the receptor domain to the catalytic domain, where it is converted into the formation of cyclic GMP. The first transduction step is the direct binding of ATP with ANF-RGC. This causes allosteric regulation of the enzyme and primes it for the activation of its catalytic moiety. The partial structural motif of the ATP binding domain in ANF-RGC has been elucidated, and it has been named ATP regulatory module (ARM). In this presentation, we provide a brief review of the ATP-regulated transduction mechanism and the ARM model. The model depicts a configuration of the ATP-binding pocket that has been experimentally validated, and the model shows that the ATP-dependent transduction process is a two- (or more) step event. The first step involves the binding of ATP with its ARM. This partially activates the cyclase and prepares it for the subsequent steps, which are consistent with its being phosphorylated and attaining the fully activated state.
authors.affiliation: Department of Cell Biology, NJMS & SOM, University of Medicine and Dentistry of New Jersey, Stratford 08084, USA. sharmark@umdnj.edu
authors.forename: R K
authors.initials: RK
authors.lastname: Sharma
authors.forename: P
authors.initials: P
authors.lastname: Yadav
authors.forename: T
authors.initials: T
authors.lastname: Duda
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000502:physiology*; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006162:Guanylate Cyclase / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017461:Receptors, Atrial Natriuretic Factor / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor