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PDBsum entry 4pgv
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Membrance protein
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PDB id
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4pgv
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DOI no:
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Science
344:1131-1135
(2014)
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PubMed id:
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Structural basis for a pH-sensitive calcium leak across membranes.
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Y.Chang,
R.Bruni,
B.Kloss,
Z.Assur,
E.Kloppmann,
B.Rost,
W.A.Hendrickson,
Q.Liu.
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ABSTRACT
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Calcium homeostasis balances passive calcium leak and active calcium uptake.
Human Bax inhibitor-1 (hBI-1) is an antiapoptotic protein that mediates a
calcium leak and is representative of a highly conserved and widely distributed
family, the transmembrane Bax inhibitor motif (TMBIM) proteins. Here, we present
crystal structures of a bacterial homolog and characterize its calcium leak
activity. The structure has a seven-transmembrane-helix fold that features two
triple-helix sandwiches wrapped around a central C-terminal helix. Structures
obtained in closed and open conformations are reversibly interconvertible by
change of pH. A hydrogen-bonded, pKa (where Ka is the acid dissociation
constant)-perturbed pair of conserved aspartate residues explains the pH
dependence of this transition, and biochemical studies show that pH regulates
calcium influx in proteoliposomes. Homology models for hBI-1 provide insights
into TMBIM-mediated calcium leak and cytoprotective activity.
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');
}
}
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