title: The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif.
abstract: The Na+/Ca2+ exchanger is a plasma membrane protein that regulates intracellular Ca2+ levels in cardiac myocytes. Transport activity is governed by Ca2+, and the primary Ca2+ sensor (CBD1) is located in a large cytoplasmic loop connecting two transmembrane helices. The binding of Ca2+ to the CBD1 sensory domain results in conformational changes that stimulate the exchanger to extrude Ca2+. Here, we present a crystal structure of CBD1 at 2.5A resolution, which reveals a novel Ca2+ binding site consisting of four Ca2+ ions arranged in a tight planar cluster. This intricate coordination pattern for a Ca2+ binding cluster is indicative of a highly sensitive Ca2+ sensor and may represent a general platform for Ca2+ sensing.
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
authors.forename: Debora A
authors.initials: DA
authors.lastname: Nicoll
authors.affiliation: Department of Chemistry and Biochemistry, UCLA-Department of Energy Center for Genomics and Proteomics, Molecular Biology Institute, University of California, Los Angeles, California 90095.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sawaya
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
authors.forename: Seunghyug
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Department of Chemistry and Biochemistry, UCLA-Department of Energy Center for Genomics and Proteomics, Molecular Biology Institute, University of California, Los Angeles, California 90095.
authors.forename: Duilio
authors.initials: D
authors.lastname: Cascio
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Philipson
authors.affiliation: Department of Physiology and the Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, California 90095. Electronic address: jabramson@mednet.ucla.edu.
authors.forename: Jeff
authors.initials: J
authors.lastname: Abramson
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D004285:Dogs; D032383:Myocytes, Cardiac / Q000737:chemistry; D011487:Protein Conformation; D044169:Receptors, Calcium-Sensing / Q000737:chemistry*; D019831:Sodium-Calcium Exchanger / Q000737:chemistry*
chemical_list: D002135:Calcium-Binding Proteins; D044169:Receptors, Calcium-Sensing; D019831:Sodium-Calcium Exchanger; D002118:Calcium