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PDBsum entry 3rb7
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Metal binding protein
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PDB id
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3rb7
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References listed in PDB file
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Key reference
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Title
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Structural basis of the ca2+ inhibitory mechanism of drosophila na+/ca2+ exchanger calx and its modification by alternative splicing.
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Authors
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M.Wu,
S.Tong,
J.Gonzalez,
V.Jayaraman,
J.L.Spudich,
L.Zheng.
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Ref.
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Structure, 2011,
19,
1509-1517.
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PubMed id
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Abstract
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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.
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