Structural studies of the Ca(2+) regulatory domain of Drosophila Na(+)/Ca (2+) exchanger CALX.
Structural studies of the Ca(2+) regulatory domain of Drosophila Na(+)/Ca (2+) exchanger CALX.
复制标题
果蝇Na( )/Ca (2 ) 交换器CALX 的Ca(2 ) 调节域的结构研究。
DOI：
10.1007/978-1-4614-4756-6_6
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发表时间：
2013
影响因子：
--
通讯作者：
Tong,Shuilong
中科院分区：
文献类型：
--
作者：
Zheng,Lei;Wu,Mousheng;Tong,Shuilong
CALX, the NCX homolog in Drosophila, involves in light-mediated Ca2+homeostasis in sensory neuronal cells. CALX exhibits a unique negative Ca2+regulatory property mediated by Ca2+ binding at its intracellular regulatory domain. Our structural studies of individual CBD1 or CBD2 domain reveal that CBD1 is the only Ca2+binding domain in CALX. Crystal structures of the entire Ca2+regulatory domain CBD12 from two alternative splicing isoforms, CALX1.1 and CALX1.2, demonstrate that CBD1 and CBD2 form an open V-shaped conformation with four Ca2+ions bound on the CBD domain interface. The structures together with Ca2+binding analyses strongly argue that the Ca2+inhibition of CALX is achieved by interdomain conformational change induced by Ca2+binding at CBD1. The conformational difference between the two isoforms also raises a hypothesis that alternative splicing residues adjust the interdomain orientation angle between CBD1 and CBD2 to modify the Ca2+regulatory property of the exchanger. These studies not only establish structural basis to understand the inhibitory Ca2+regulation and the alternative splicing modification of CALX, but also shed light on the general Ca2+regulatory mechanism of other mammalian NCX proteins.
