
<ArticleTitle>Allosteric activation of a <prot>spring-loaded natriuretic peptide receptor</prot> dimer by hormone.</ArticleTitle>
<AbstractText><prot>Natriuretic peptides</prot> (<prot>NPs</prot>) are <prot>vasoactive cyclic-peptide hormones</prot> important in blood pressure regulation through interaction with natriuretic cell-surface receptors. We report the hormone-binding thermodynamics and crystal structures at 2.9 and 2.0 angstroms, respectively, of the extracellular domain of the unliganded human <prot>NP receptor</prot> (<prot>NPR-C</prot>) and its complex with <prot>CNP</prot>, a 22-amino acid <prot>NP</prot>. A single <prot>CNP</prot> molecule is bound in the interface of an <prot>NPR-C</prot> dimer, resulting in asymmetric interactions between the hormone and the symmetrically related receptors. Hormone binding induces a 20 angstrom closure between the membrane-proximal domains of the dimer. In each monomer, the opening of an interdomain cleft, which is tethered together by a linker peptide acting as a molecular spring, is likely a conserved allosteric trigger for intracellular signaling by the natriuretic receptor family.</AbstractText>
