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J Mol Biol. 2008 Mar 28;377(3):945-55. doi: 10.1016/j.jmb.2008.01.046. Epub 2008 Jan 30.

Structure and dynamics of Ca2+-binding domain 1 of the Na+/Ca2+ exchanger in the presence and in the absence of Ca2+.

Author information

1
Department of Chemistry and Biochemistry and National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32306, USA.

Abstract

The Na(+)/Ca(2+) exchanger is the major exporter of Ca(2+) across the cell membrane of cardiomyocytes. The activity of the exchanger is regulated by a large intracellular loop that contains two Ca(2+)-binding domains, calcium-binding domain (CBD) 1 and CBD2. CBD1 binds Ca(2+) with much higher affinity than CBD2 and is considered to be the primary Ca(2+) sensor. The effect of Ca(2+) on the structure and dynamics of CBD1 has been characterized by NMR spectroscopy using chemical shifts, residual dipolar couplings, and spin relaxation. Residual dipolar couplings are used in a new way for residue selection in the determination of the anisotropic rotational diffusion tensor from spin relaxation data. The results provide a highly consistent description across these complementary data sets and show that Ca(2+) binding is accompanied by a selective conformational change among the binding site residues. Residues that exhibit a significant conformational change are also sites of altered dynamics. In particular, Ca(2+) binding restricts the mobility of the major acidic segment and affects the dynamics of several nearby binding loops. These observations indicate that Ca(2+) elicits a local transition to a well-ordered coordination geometry in the CBD1-binding site.

PMID:
18280495
PMCID:
PMC2702724
DOI:
10.1016/j.jmb.2008.01.046
[Indexed for MEDLINE]
Free PMC Article

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