Publication Abstract from PubMed
The Na(+)/Ca(2+) exchanger CALX promotes Ca(2+) efflux in Drosophila sensory neuronal cells to facilitate light-mediated Ca(2+) homeostasis. CALX activity is negatively regulated by specific Ca(2+) interaction within its two intracellular Ca(2+) regulatory domains CBD1 and CBD2, yet how the Ca(2+) binding is converted to molecular motion to operate the exchanger is unknown. Here, we report crystal structures of the entire Ca(2+) regulatory domain CBD12 from two alternative splicing isoforms, CALX 1.1 and 1.2, exhibiting distinct regulatory Ca(2+) dependency. The structures show an open V-shaped conformation with four Ca(2+) ions bound on the CBD domain interface, confirmed by LRET analysis. The structures together with Ca(2+)-binding analysis support that the Ca(2+) inhibition of CALX is achieved by interdomain conformational changes induced by Ca(2+) binding at CBD1. The conformational difference between the two isoforms also indicates that alternative splicing adjusts the interdomain orientation angle to modify the Ca(2+) regulatory property of the exchangers.
Structural Basis of the Ca(2+) Inhibitory Mechanism of Drosophila Na(+)/Ca(2+) Exchanger CALX and Its Modification by Alternative Splicing.,Wu M, Tong S, Gonzalez J, Jayaraman V, Spudich JL, Zheng L Structure. 2011 Oct 12;19(10):1509-17. PMID:22000518[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
