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Structural Studies of the Ca2+ Regulatory Domain of Drosophila Na+/Ca2+ Exchanger CALX

  • Lei ZhengEmail author
  • Mousheng Wu
  • Shuilong Tong
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 961)

Abstract

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.

Keywords

Drosophila CALX Sodium-calcium exchange 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Center for Membrane Biology, Department of Biochemistry and Molecular BiologyThe University of Texas Houston Medical SchoolHoustonUSA

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