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PDBsum entry 4mvs
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Metal transport
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PDB id
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4mvs
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References listed in PDB file
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Key reference
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Title
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Structural basis for ca2+ selectivity of a voltage-Gated calcium channel.
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Authors
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L.Tang,
T.M.Gamal el-Din,
J.Payandeh,
G.Q.Martinez,
T.M.Heard,
T.Scheuer,
N.Zheng,
W.A.Catterall.
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Ref.
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Nature, 2014,
505,
56-61.
[DOI no: ]
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PubMed id
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Abstract
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Voltage-gated calcium (CaV) channels catalyse rapid, highly selective influx of
Ca(2+) into cells despite a 70-fold higher extracellular concentration of Na(+).
How CaV channels solve this fundamental biophysical problem remains unclear.
Here we report physiological and crystallographic analyses of a calcium
selectivity filter constructed in the homotetrameric bacterial NaV channel
NaVAb. Our results reveal interactions of hydrated Ca(2+) with two high-affinity
Ca(2+)-binding sites followed by a third lower-affinity site that would
coordinate Ca(2+) as it moves inward. At the selectivity filter entry, Site 1 is
formed by four carboxyl side chains, which have a critical role in determining
Ca(2+) selectivity. Four carboxyls plus four backbone carbonyls form Site 2,
which is targeted by the blocking cations Cd(2+) and Mn(2+), with single
occupancy. The lower-affinity Site 3 is formed by four backbone carbonyls alone,
which mediate exit into the central cavity. This pore architecture suggests a
conduction pathway involving transitions between two main states with one or two
hydrated Ca(2+) ions bound in the selectivity filter and supports a 'knock-off'
mechanism of ion permeation through a stepwise-binding process. The multi-ion
selectivity filter of our CaVAb model establishes a structural framework for
understanding the mechanisms of ion selectivity and conductance by vertebrate
CaV channels.
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