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PDBsum entry 1s1e
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Transport protein
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PDB id
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1s1e
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References listed in PDB file
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Key reference
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Title
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Two n-Terminal domains of kv4 k(+) channels regulate binding to and modulation by kchip1.
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Authors
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R.H.Scannevin,
K.Wang,
F.Jow,
J.Megules,
D.C.Kopsco,
W.Edris,
K.C.Carroll,
Q.Lü,
W.Xu,
Z.Xu,
A.H.Katz,
S.Olland,
L.Lin,
M.Taylor,
M.Stahl,
K.Malakian,
W.Somers,
L.Mosyak,
M.R.Bowlby,
P.Chanda,
K.J.Rhodes.
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Ref.
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Neuron, 2004,
41,
587-598.
[DOI no: ]
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PubMed id
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Abstract
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The family of calcium binding proteins called KChIPs associates with Kv4 family
K(+) channels and modulates their biophysical properties. Here, using
mutagenesis and X-ray crystallography, we explore the interaction between Kv4
subunits and KChIP1. Two regions in the Kv4.2 N terminus, residues 7-11 and
71-90, are necessary for KChIP1 modulation and interaction with Kv4.2. When
inserted into the Kv1.2 N terminus, residues 71-90 of Kv4.2 are also sufficient
to confer association with KChIP1. To provide a structural framework for these
data, we solved the crystal structures of Kv4.3N and KChIP1 individually. Taken
together with the mutagenesis data, the individual structures suggest that that
the Kv4 N terminus is required for stable association with KChIP1, perhaps
through a hydrophobic surface interaction, and that residues 71-90 in Kv4
subunits form a contact loop that mediates the specific association of KChIPs
with Kv4 subunits.
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Figure 1.
Figure 1. The Proximal N Terminus of Kv4.2 Is Necessary for
Modulation by KChIP1Currents were recorded from oocytes injected
with the indicated Kv4.2 wild-type or deletion mutant RNA in the
presence or absence of KChIP1. The left side panels depict
representative current traces measured at +50 mV for 1 s from
holding potential at −80 mV, and the right side of each panel
depicts normalized recovery from inactivation fitted with a
single exponential function for Kv4.2 alone (open circle) and
for Kv4.2 co-expressed with KChIP1 (closed circle).(A) Wild-type
Kv4.2; (B) Kv4.2Δ2–21; (C) Kv4.2Δ2–11; (D) Kv4.2Δ2–6;
(E) Kv4.2Δ7–11; (F) Kv4.2(WGEFA) multiple point mutant,
contains mutations in Kv4.2 7–11 region.
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Figure 2.
Figure 2. Residues 71–90 of Kv4.2N Are Critical for
KChIP1 ModulationCurrents were recorded as in Figure 1. The left
side of all panels depicts representative current traces from
oocytes injected with indicated Kv4.2 RNA in the presence or
absence of KChIP1. Right side of each panel depicts
normalized recovery from inactivation fitted with a single
exponential function for Kv4.2 alone (open circle) and for Kv4.2
co-expressed with KChIP1 (closed circle).(A) Kv4.2Δ161–180;
(B) Kv4.2Δ71–90; (C) Kv4.2 (F74R) single point mutant.
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The above figures are
reprinted
by permission from Cell Press:
Neuron
(2004,
41,
587-598)
copyright 2004.
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