The Crystal Structure of the Primary Ca2+ Sensor of the Na+/Ca2+ Exchanger Reveals a Novel Ca2+ Binding Motif

• DOI: 10.1074/jbc.c600117200
• Publication Date: 2006-06-15T00:29:20Z
• Authors: Debora A. Nicoll; Michael R. Sawaya; Seunghyug Kwon; Duilio Cascio; Kenneth D. Philipson; Jeff Abramson
• Keywords: 0301 basic medicine; Binding Sites; Protein Conformation; Calcium-Binding Proteins; Crystallography, X-Ray; Sodium-Calcium Exchanger; 03 medical and health sciences; Dogs; Animals; Calcium; Myocytes, Cardiac; Crystallization; Receptors, Calcium-Sensing

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.