1yk0

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spinqualitylabelsall models 1yk0, resolution 2.4Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

structure of natriuretic peptide receptor-C complexed with atrial natriuretic peptide

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Cardiovascular homeostasis and blood pressure regulation are reliant, in, part, on interactions between natriuretic peptide (NP) hormones and, natriuretic peptide receptors (NPR). The C-type NPR (NPR-C) is responsible, for clearance of NP hormones from the circulation, and displays a, cross-reactivity for all NP hormones (ANP, BNP, and CNP), in contrast to, other NPRs, which are more restricted in their specificity. In order to, elucidate the structural determinants for the binding specificity and, cross-reactivity of NPR-C with NP hormones, we have determined the crystal, structures of the complexes of NPR-C with atrial natriuretic peptide, (ANP), and with brain natriuretic peptide (BNP). A structural comparison, of these complexes, with the previous structure of the NPR-C/CNP complex, reveals that NPR-C uses a conformationally inflexible surface to bind, three different, highly flexible, NP ligands. The complex structures, support a mechanism of rigid promiscuity rather than conformational, plasticity by the receptor. While ANP and BNP appear to adopt similar, receptor-bound conformations, the CNP structure diverges, yet shares sets, of common receptor contacts with the other ligands. The degenerate versus, selective hormone recognition properties of different NPRs appears to, derive largely from two cavities on the receptor surfaces, pocket I and, pocket II, that serve as anchoring sites for hormone side-chains and, modulate receptor selectivity.

Disease

Known diseases associated with this structure: Acromesomelic dysplasia, Maroteaux type OMIM:[108961], Hypertension, salt-resistant (1) OMIM:[108962]

About this Structure

1YK0 is a Protein complex structure of sequences from Homo sapiens with NAG and CL as ligands. Full crystallographic information is available from OCA.

Reference

Structural determinants of natriuretic peptide receptor specificity and degeneracy., He XL, Dukkipati A, Garcia KC, J Mol Biol. 2006 Aug 25;361(4):698-714. Epub 2006 Jul 10. PMID:16870210

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