Structural Basis for Ca2+ Regulation in the Na+/Ca2+ Exchanger.
From: Department of Biophysical Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands. hilge@nmr.ru.nl
Annals of the New York Academy of Sciences
- Publish Date: Mar 2007
- ISSN: 0077-8923
- Volume: 1099
- Issue:
- Pages: 7-15
- Medium: Print
- Language: English
- Citation (JAMA): Hilge Mark, Aelen Jan, Perrakis Anastassis, et al. Structural Basis for Ca2+ Regulation in the Na+/Ca2+ Exchanger.. Ann. N. Y. Acad. Sci. Mar 2007;1099:7-15
Abstract
Binding of Na+ and Ca2+ ions to the large cytosolic loop of the Na+/Ca2+ exchanger (NCX) regulates its ion transport across the plasma membrane. 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 constitute a novel Ca2+-binding motif and are very similar in the Ca2+-bound state. Strikingly, in the absence of Ca2+ the upper half of CBD1 unfolds while CBD2 maintains its structural integrity. Together with a sevenfold 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.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Binding Sites, Calcium, Dogs, Models, Molecular, Molecular Sequence Data, Protein Conformation, Sequence Homology, Amino Acid, Sodium-Calcium Exchanger
Check for Full Text / PubMed Unique Identifier (PMID): 17347334
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