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Peptides. 2005 Jun;26(6):1035-43. Epub 2005 Apr 7.

A new paradigm for hormone recognition and allosteric receptor activation revealed from structural studies of NPR-C.

Author information

1
Department of Microbiology & Immunology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305-5124, USA.

Abstract

The natriuretic peptide system of hormones and receptors poses an abundance of interesting biophysical questions regarding receptor structure, hormone recognition, and receptor activation. Functional and biochemical data have implicated a series of conformational changes as the mechanism by which NP receptor activation is achieved. We have explored the structural basis of hormone recognition by the NP clearance receptor, termed NPR-C. While NPR-C does not contain the classical guanylyl-cyclase activity in its intracellular domains, its extracellular domain is highly similar to the GC-coupled members of this family. The 1:2 stoichiometry of hormone binding to NPR-C is also used by NPR-A and -B to bind hormones. The structure of NPR-C in both quiescent and hormone-bound forms reveals the hormone intercalates within the interface of a receptor dimer, inducing a large-scale conformational change in the membrane proximal regions. This mechanism of hormone recognition will be conserved across the entire NPR family. The allosteric response of the NPR-C ectodomain to ligand binding is likely a glimpse of the general activation signal of these receptors, despite their differing downstream signaling cascades. In this review, we discuss our results on NPR-C and their relevance to the NPR family as a whole, as well as its place as a basic new paradigm for receptor activation.

PMID:
15911071
DOI:
10.1016/j.peptides.2004.08.035
[Indexed for MEDLINE]

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