Structural basis of the Ca2+ inhibitory mechanism of Drosophila Na+/Ca2+ exchanger CALX and its modification by alternative splicing.
Structural basis of the Ca2+ inhibitory mechanism of Drosophila Na+/Ca2+ exchanger CALX and its modification by alternative splicing.
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DOI：
10.1016/j.str.2011.07.008
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发表时间：
2011-10-12
期刊：
影响因子：
5.7
通讯作者：
Zheng, Lei
中科院分区：
文献类型：
--
作者：
Wu, Mousheng;Tong, Shuilong;Gonzalez, Jennifer;Jayaraman, Vasanthi;Spudich, John L.;Zheng, Lei
The Na+/Ca2+ exchanger CALX promotes Ca2+ efflux in Drosophila sensory neuronal cells to facilitate light-mediated Ca2+ homeostasis. CALX activity is negatively regulated by specific Ca2+ interaction within its two intracellular Ca2+ regulatory domains CBD1 and CBD2, yet how the Ca2+ binding is converted to molecular motion to operate the exchanger is unknown. Here we report crystal structures of the entire Ca2+ regulatory domain CBD12 from two alternative splicing isoforms, CALX, 1.1 and 1.2, exhibiting distinct regulatory Ca2+-dependency. The structures show an open V-shaped conformation with four Ca2+ ions bound on the CBD domain interface, confirmed by LRET analysis. The structures together with Ca2+ binding analysis support that the Ca2+ inhibition of CALX is achieved by interdomain conformational changes induced by Ca2+ binding at CBD1. The conformational difference between the two isoforms also indicates that alternative splicing adjusts the interdomain orientation angle to modify the Ca2+ regulatory property of the exchangers.
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