PDBsum entry 3rb5

Metal binding protein

PDB id: 3rb5

Contents

Protein chains

238 a.a.

Ligands

MPD

SO4 ×7

Metals

_CA ×8

Waters ×42

PDB id:

3rb5

Name:

Metal binding protein

Title:

Crystal structure of calcium binding domain cbd12 of calx1.1

Structure:

Na/ca exchange protein. Chain: a, b. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: calx, ncx, cg5685. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.35Å R-factor: 0.219 R-free: 0.258

Authors:

M.Wu,L.Zheng

Key ref:

M.Wu et al. (2011). Structural basis of the Ca2+ inhibitory mechanism of Drosophila Na+/Ca2+ exchanger CALX and its modification by alternative splicing. Structure, 19, 1509-1517. PubMed id: 22000518

Date:

28-Mar-11 Release date: 02-Nov-11

Protein chains

Q9VDG5  (Q9VDG5_DROME) -  Sodium/calcium exchanger Calx from Drosophila melanogaster

Seq: 950 a.a.

Struc: 238 a.a.

Enzyme reactions

• Enzyme class: E.C.?

Structure 19:1509-1517 (2011)

PubMed id: 22000518

Structural basis of the Ca2+ inhibitory mechanism of Drosophila Na+/Ca2+ exchanger CALX and its modification by alternative splicing.

M.Wu, S.Tong, J.Gonzalez, V.Jayaraman, J.L.Spudich, L.Zheng.

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.