Structural highlights
Function
NAC1_CANLF Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:1700476, PubMed:1785844, PubMed:9486131, PubMed:17962412). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions (By similarity).[UniProtKB:P70414][1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors.,Hilge M, Aelen J, Vuister GW Mol Cell. 2006 Apr 7;22(1):15-25. PMID:16600866[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nicoll DA, Longoni S, Philipson KD. Molecular cloning and functional expression of the cardiac sarcolemmal Na(+)-Ca2+ exchanger. Science. 1990 Oct 26;250(4980):562-5. PMID:1700476
- ↑ Nicoll DA, Philipson KD. Molecular studies of the cardiac sarcolemmal sodium-calcium exchanger. Ann N Y Acad Sci. 1991;639:181-8. PMID:1785844
- ↑ Besserer GM, Ottolia M, Nicoll DA, Chaptal V, Cascio D, Philipson KD, Abramson J. The second Ca2+-binding domain of the Na+ Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18467-72. Epub 2007 Oct 25. PMID:17962412
- ↑ Chaptal V, Ottolia M, Mercado-Besserer G, Nicoll DA, Philipson KD, Abramson J. Structure and functional analysis of a Ca2+ sensor mutant of the Na+/Ca2+ exchanger. J Biol Chem. 2009 May 29;284(22):14688-92. Epub 2009 Mar 30. PMID:19332552 doi:10.1074/jbc.C900037200
- ↑ Linck B, Qiu Z, He Z, Tong Q, Hilgemann DW, Philipson KD. Functional comparison of the three isoforms of the Na+/Ca2+ exchanger (NCX1, NCX2, NCX3). Am J Physiol. 1998 Feb;274(2 Pt 1):C415-23. PMID:9486131
- ↑ Hilge M, Aelen J, Vuister GW. Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors. Mol Cell. 2006 Apr 7;22(1):15-25. PMID:16600866 doi:10.1016/j.molcel.2006.03.008
