Title : Structure of the dimerized hormone-binding
domain of a guanylyl-cyclase-coupled
receptor
Abstract :
- The atrial natriuretic peptide ( ANP ) hormone is secreted by the heart in response to an increase in blood pressure
- ANP exhibits several potent anti-hypertensive actions in the kidney, adrenal gland and vascular system
- These actions are induced by hormone binding extracellularly to the ANP receptor , thereby activating its intracellular guanylyl cyclase domain for the production of cyclic GMP
- Here we present the crystal structure of the glycosylated dimerized hormone-binding domain of the ANP receptor at 2.0-A resolution
- The monomer comprises two interconnected subdomains , each encompassing a central beta-sheet flanked by alpha-helices, and exhibits the type I periplasmic binding protein fold
- Dimerization is mediated by the juxta position of four parallel helices, arranged two by two, which brings the two protruding carboxy termini into close relative proximity
- From affinity labelling and mutagenesis studies, the ANP-binding site maps to the side of the dimer crevice and extends to near the dimer interface
- A conserved chloride-binding site is located in the membrane distal domain , and we found that hormone binding is chloride dependent
- These studies suggest mechanisms for hormone activation and the allostery of the ANP receptor