title: Structure and dynamics of Ca2+-binding domain 1 of the Na+/Ca2+ exchanger in the presence and in the absence of Ca2+.
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.
authors.affiliation: Department of Chemistry and Biochemistry and National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Johnson
authors.forename: Lei
authors.initials: L
authors.lastname: Bruschweiler-Li
authors.forename: Scott A
authors.initials: SA
authors.lastname: Showalter
authors.forename: Geerten W
authors.initials: GW
authors.lastname: Vuister
authors.forename: Fengli
authors.initials: F
authors.lastname: Zhang
authors.forename: Rafael
authors.initials: R
authors.lastname: Brüschweiler
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry*; D004285:Dogs; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D019831:Sodium-Calcium Exchanger / Q000737:chemistry*
chemical_list: D011994:Recombinant Proteins; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D002118:Calcium