2FWS

First Ca2+ binding domain of the Na,Ca-exchanger (NCX1)

Summary for 2FWS

• Entry DOI: 10.2210/pdb2fws/pdb
• Related: 2fwu
• NMR Information: BMRB: 7009
• Descriptor: Sodium/calcium exchanger 1, CALCIUM ION (2 entities in total)
• Functional Keywords: beta-sandwich, greek key, cis-proline, beta-bulge, ca2+ binding, metal transport regulator
• Biological source: Canis lupus familiaris (dog)
• Cellular location: Cell membrane; Multi-pass membrane protein: P23685
• Total number of polymer chains: 1
• Total formula weight: 15243.67

Authors

Hilge, M.,Aelen, J.,Vuister, G.W. (deposition date: 2006-02-03, release date: 2006-04-18, Last modification date: 2024-05-29)

Primary citation

Hilge, M.,Aelen, J.,Vuister, G.W.
Ca(2+) regulation in the na(+)/ca(2+) exchanger involves two markedly different ca(2+) sensors
Mol.Cell, 22:15-25, 2006

PubMed Abstract: The plasma membrane Na+/Ca2+ exchanger (NCX) is almost certainly the major Ca2+ extrusion mechanism in cardiac myocytes. Binding of Na+ and Ca2+ ions to its large cytosolic loop regulates ion transport of the exchanger. We determined the solution structures of two Ca2+ binding domains (CBD1 and CBD2) that, together with an alpha-catenin-like domain (CLD), form the regulatory exchanger loop. CBD1 and CBD2 are very similar in the Ca2+ bound state and describe the Calx-beta motif. Strikingly, in the absence of Ca2+, the upper half of CBD1 unfolds while CBD2 maintains its structural integrity. Together with a 7-fold higher affinity for Ca2+, this suggests that CBD1 is the primary Ca2+ sensor. Specific point mutations in either domain largely allow the interchange of their functionality and uncover the mechanism underlying Ca2+ sensing in NCX.

PubMed: 16600866
DOI: 10.1016/j.molcel.2006.03.008

Experimental method

SOLUTION NMR