3RB5

Crystal structure of calcium binding domain CBD12 of CALX1.1

Summary for 3RB5

• Entry DOI: 10.2210/pdb3rb5/pdb
• Related: 3RB7
• Descriptor: Na/Ca exchange protein, CALCIUM ION, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (5 entities in total)
• Functional Keywords: cbd12, calcium binding and regulation, metal binding protein
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 2
• Total formula weight: 68524.31

Authors

Wu, M.,Zheng, L. (deposition date: 2011-03-28, release date: 2011-11-02, Last modification date: 2024-02-21)

Primary citation

Wu, M.,Tong, S.,Gonzalez, J.,Jayaraman, V.,Spudich, J.L.,Zheng, L.
Structural Basis of the Ca(2+) Inhibitory Mechanism of Drosophila Na(+)/Ca(2+) Exchanger CALX and Its Modification by Alternative Splicing.
Structure, 19:1509-1517, 2011

PubMed 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.

PubMed: 22000518
DOI: 10.1016/j.str.2011.07.008

Experimental method

X-RAY DIFFRACTION (2.35 Å)