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Title: Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

Abstract

Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft,more » thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.« less

Authors:
; ; ; ; ; ;  [1];  [2];  [2]
  1. (Biosciences Division)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH); Canadian Inst. for Health and Research; Canada Foundation for Innovation; Alberta Scienc and Research Instruments Program
OSTI Identifier:
1014869
Report Number(s):
ANL/BIO/JA-70111
Journal ID: ISSN 1742-464X; TRN: US201111%%389
DOE Contract Number:  
DE-AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: The FEBS J.; Journal Volume: 278; Journal Issue: 1 ; Jun. 2011
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; ALGAE; BLOOD; BLOOD PRESSURE; BLOOD VESSELS; CRYSTAL STRUCTURE; CYCLASES; HORMONES; PEPTIDES; REGULATIONS; ROTATION; STIMULATION

Citation Formats

Misono, K. S., Philo, J. S., Arakawa, T., Ogata, C. M., Qiu, Y., Ogawa, H., Young, H. S., Univ. of Nevada), and Alliance Protein Labs.). Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.. United States: N. p., 2011. Web. doi:10.1111/j.1742-4658.2011.08083.x.
Misono, K. S., Philo, J. S., Arakawa, T., Ogata, C. M., Qiu, Y., Ogawa, H., Young, H. S., Univ. of Nevada), & Alliance Protein Labs.). Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.. United States. doi:10.1111/j.1742-4658.2011.08083.x.
Misono, K. S., Philo, J. S., Arakawa, T., Ogata, C. M., Qiu, Y., Ogawa, H., Young, H. S., Univ. of Nevada), and Alliance Protein Labs.). Wed . "Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.". United States. doi:10.1111/j.1742-4658.2011.08083.x.
@article{osti_1014869,
title = {Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.},
author = {Misono, K. S. and Philo, J. S. and Arakawa, T. and Ogata, C. M. and Qiu, Y. and Ogawa, H. and Young, H. S. and Univ. of Nevada) and Alliance Protein Labs.)},
abstractNote = {Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.},
doi = {10.1111/j.1742-4658.2011.08083.x},
journal = {The FEBS J.},
number = 1 ; Jun. 2011,
volume = 278,
place = {United States},
year = {Wed Jun 01 00:00:00 EDT 2011},
month = {Wed Jun 01 00:00:00 EDT 2011}
}