Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone

X. L. He, D. C. Chow, M. M. Martick, K. C. Garcia*

*Corresponding author for this work

Research output: Contribution to journalArticle

130 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1657-1662
Number of pages6
JournalScience
Volume293
Issue number5535
DOIs
StatePublished - Aug 31 2001

ASJC Scopus subject areas

  • General

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