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PDBsum entry 4p60
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Transport protein
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PDB id
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4p60
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References listed in PDB file
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Key reference
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Title
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Calcium-Induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers.
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Authors
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C.Thangaratnarajah,
J.J.Ruprecht,
E.R.Kunji.
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Ref.
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Nat Commun, 2014,
5,
5491.
[DOI no: ]
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PubMed id
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Abstract
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The transport activity of human mitochondrial aspartate/glutamate carriers is
central to the malate-aspartate shuttle, urea cycle, gluconeogenesis and myelin
synthesis. They have a unique three-domain structure, comprising a
calcium-regulated N-terminal domain with eight EF-hands, a mitochondrial carrier
domain, and a C-terminal domain. Here we present the calcium-bound and
calcium-free structures of the N- and C-terminal domains, elucidating the
mechanism of calcium regulation. Unexpectedly, EF-hands 4-8 are involved in
dimerization of the carrier and form a static unit, whereas EF-hands 1-3 form a
calcium-responsive mobile unit. On calcium binding, an amphipathic helix of the
C-terminal domain binds to the N-terminal domain, opening a vestibule. In the
absence of calcium, the mobile unit closes the vestibule. Opening and closing of
the vestibule might regulate access of substrates to the carrier domain, which
is involved in their transport. These structures provide a framework for
understanding cases of the mitochondrial disease citrin deficiency.
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