Title : Allosteric activation of a spring-loaded natriuretic peptide receptor
dimer by hormone
Abstract :
- Natriuretic peptides ( NPs ) are vasoactive cyclic-peptide hormones 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 NP receptor ( NPR-C ) and its complex with CNP , a 22-amino acid NP
- A single CNP molecule is bound in the interface of an NPR-C 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