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PDBsum entry 3e9u
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Membrane protein
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PDB id
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3e9u
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References listed in PDB file
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Key reference
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Title
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Crystal structure of cbd2 from the drosophila na(+)/ca(2+) exchanger: diversity of ca(2+) regulation and its alternative splicing modification.
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Authors
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M.Wu,
M.Wang,
J.Nix,
L.V.Hryshko,
L.Zheng.
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Ref.
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J Mol Biol, 2009,
387,
104-112.
[DOI no: ]
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PubMed id
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Abstract
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Na(+)/Ca(2+) exchangers (NCXs) promote the extrusion of intracellular Ca(2+) to
terminate numerous Ca(2+)-mediated signaling processes. Ca(2+) interaction at
two Ca(2+) binding domains (CBDs; CBD1 and CBD2) is important for tight
regulation of the exchange activity. Diverse Ca(2+) regulatory properties have
been reported with several NCX isoforms; whether the regulatory diversity of
NCXs is related to structural differences of the pair of CBDs is presently
unknown. Here, we reported the crystal structure of CBD2 from the Drosophila
melanogaster exchanger CALX1.1. We show that the CALX1.1-CBD2 is an
immunoglobulin-like structure, similar to mammalian NCX1-CBD2, but the predicted
Ca(2+) interaction region of CALX1.1-CBD2 is arranged in a manner that precludes
Ca(2+) binding. The carboxylate residues that coordinate two Ca(2+) in the
NCX1-CBD1 structure are neutralized by two Lys residues in CALX1.1-CBD2. This
structural observation was further confirmed by isothermal titration
calorimetry. The CALX1.1-CBD2 structure also clearly shows the alternative
splicing region forming two adjacent helices perpendicular to CBD2. Our results
provide structural evidence that the diversity of Ca(2+) regulatory properties
of NCX proteins can be achieved by (1) local structure rearrangement of Ca(2+)
binding site to change Ca(2+) binding properties of CBD2 and (2) alternative
splicing variation altering the protein domain-domain conformation to modulate
the Ca(2+) regulatory behavior.
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Figure 1.
Fig. 1. Overall structure of the CBD2 domain. The CBD2
structure of CALX1.1 was superimposed on the Ca^2+-bound CBD2
structure of canine NCX1(PDB code: 2QVM). Both structures were
rendered as ribbons. The NCX1 structure is colored gray and
β-strands A–G of CALX1.1 have rainbow colors. The residues in
the alterative splicing region of CALX1.1-CBD2 are highlighted
as stick–balls.
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Figure 2.
Fig. 2. Stereo view of the pseudo-Ca^2+ binding region in the
CALX1.1-CBD2 structure. The structure of CALX1.1-CBD2, shown as
cyan ribbons, is superimposed onto the Ca^2+-bound NCX1-CBD2,
shown as wheat ribbons. The residues in the predicted Ca^2+
binding site are depicted as stick–balls; the N/O atoms are
colored blue/red. Salt bridge and hydrogen bonds in CALX1.1-CBD2
are displayed as yellow broken lines. Two Ca^2+ positions from
the NCX1 structure are drawn as green spheres. The residues from
NCX1 are underlined and italicized.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2009,
387,
104-112)
copyright 2009.
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