tailieunhanh - Báo cáo khoa học: Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase

Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natri-uresis 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 cen-tral role in cardiovascular regulation. | ịFEBS Journal MINIREVIEW Structure signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase Kunio S. Misono1 John S. Philo2 Tsutomu Arakawa2 Craig M. Ogata3 Yue Qiu1 Haruo Ogawa1 and Howard S. Young4 1 University of Nevada Schoolof Medicine Reno NV USA 2 Alliance Protein Laboratories Thousand Oaks CA USA 3 Advance Photon Source Argonne NationalLaboratory Argonne IL USA 4 Department of Biochemistry University of Alberta Edmonton AL Canada Keywords allosteric regulation atrialnatriuretic peptide receptor guanylylcyclase hormone binding natriuretic peptides single transmembrane segment receptor single-particle electron microscopy structuralmotif transmembrane signal transduction X-ray crystallography Correspondence K. S. Misono Department of Biochemistry University of Nevada Schoolof Medicine Reno Nevada 89557 USA Fax 1 775 784 1419 Tel 1 775 784 4690 E-mail kmisono@ Present address Institute of Molecular and Cellular Biosciences University of Tokyo Tokyo Japan Received 10 September 2010 revised 30 December 2010 accepted 2 March 2011 doi Atrial natriuretic peptide ANP and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natri-uresis 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 .

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