NDLI: Structural basis of the $Ca^{2+}$ inhibitory mechanism of Drosophila $Na^{+}/Ca^{2+}$ exchanger CALX and its modification by alternative splicing

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wu, Mousheng Tong, Shuilong Gonzalez, Jennifer Jayaraman, Vasanthi Spudich, John L. Zheng, Lei
Description	Country affiliation: United States Author Affiliation: Wu M ( Center for Membrane Biology, Department of Biochemistry and Molecular Biology, The University of Texas Houston Medical School, Houston, TX 77030, USA.)
Abstract	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.
File Format	HTM / HTML
ISSN	09692126
e-ISSN	18784186
DOI	10.1016/j.str.2011.07.008
Journal	Structure
Issue Number	10
Volume Number	19
Language	English
Publisher	Elsevier
Publisher Date	2011-10-12
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Molecular Biology Discipline Biochemistry Discipline Biotechnology Alternative Splicing Antiporters Chemistry Drosophila Proteins Drosophila Amino Acid Sequence Animals Binding Sites Calcium Chromatography, Gel Cloning, Molecular Escherichia Coli Genetics Metabolism Fluorescence Models, Molecular Molecular Sequence Data Protein Binding Protein Conformation Protein Isoforms Sequence Homology, Amino Acid Sodium-calcium Exchanger Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Structural Biology Molecular Biology

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