Structural studies of the Ca(2+) regulatory domain of Drosophila Na(+)/Ca (2+) exchanger CALX.

Abstract:

:CALX, the NCX homolog in Drosophila, involves in light-mediated Ca(2+) homeostasis in sensory neuronal cells. CALX exhibits a unique negative Ca(2+) 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 Ca(2+) binding domain in CALX. Crystal structures of the entire Ca(2+) 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 Ca(2+) ions bound on the CBD domain interface. The structures together with Ca(2+) binding analyses strongly argue that the Ca(2+) inhibition of CALX is achieved by interdomain conformational change induced by Ca(2+) 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 Ca(2+) regulatory property of the exchanger. These studies not only establish structural basis to understand the inhibitory Ca(2+) regulation and the alternative splicing modification of CALX, but also shed light on the general Ca(2+) regulatory mechanism of other mammalian NCX proteins.

journal_name

Adv Exp Med Biol

authors

Zheng L,Wu M,Tong S

doi

10.1007/978-1-4614-4756-6_6

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

55-63

eissn

0065-2598

issn

2214-8019

journal_volume

961

pub_type

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