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PDBsum entry 4kjs
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Transport protein
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PDB id
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4kjs
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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 ca2+/h+ antiporter protein yfke reveals the mechanisms of ca2+ efflux and its ph regulation.
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Authors
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M.Wu,
S.Tong,
S.Waltersperger,
K.Diederichs,
M.Wang,
L.Zheng.
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Ref.
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Proc Natl Acad Sci U S A, 2013,
110,
11367-11372.
[DOI no: ]
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PubMed id
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Abstract
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Ca(2+) efflux by Ca(2+) cation antiporter (CaCA) proteins is important for
maintenance of Ca(2+) homeostasis across the cell membrane. Recently, the
monomeric structure of the prokaryotic Na(+)/Ca(2+) exchanger (NCX) antiporter
NCX_Mj protein from Methanococcus jannaschii shows an outward-facing
conformation suggesting a hypothesis of alternating substrate access for Ca(2+)
efflux. To demonstrate conformational changes essential for the CaCA mechanism,
we present the crystal structure of the Ca(2+)/H(+) antiporter protein YfkE from
Bacillus subtilis at 3.1-Å resolution. YfkE forms a homotrimer, confirmed by
disulfide crosslinking. The protonated state of YfkE exhibits an inward-facing
conformation with a large hydrophilic cavity opening to the cytoplasm in each
protomer and ending in the middle of the membrane at the Ca(2+)-binding site. A
hydrophobic "seal" closes its periplasmic exit. Four conserved
α-repeat helices assemble in an X-like conformation to form a Ca(2+)/H(+)
exchange pathway. In the Ca(2+)-binding site, two essential glutamate residues
exhibit different conformations compared with their counterparts in NCX_Mj,
whereas several amino acid substitutions occlude the Na(+)-binding sites. The
structural differences between the inward-facing YfkE and the outward-facing
NCX_Mj suggest that the conformational transition is triggered by the rotation
of the kink angles of transmembrane helices 2 and 7 and is mediated by large
conformational changes in their adjacent transmembrane helices 1 and 6. Our
structural and mutational analyses not only establish structural bases for
mechanisms of Ca(2+)/H(+) exchange and its pH regulation but also shed light on
the evolutionary adaptation to different energy modes in the CaCA protein family.
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