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PDBsum entry 2nz0
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Membrane protein
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PDB id
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2nz0
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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 modulation of kv4 k+ channels by auxiliary kchip subunits.
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Authors
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H.Wang,
Y.Yan,
Q.Liu,
Y.Huang,
Y.Shen,
L.Chen,
Y.Chen,
Q.Yang,
Q.Hao,
K.Wang,
J.Chai.
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Ref.
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Nat Neurosci, 2007,
10,
32-39.
[DOI no: ]
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PubMed id
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Abstract
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KChIPs coassemble with pore-forming Kv4 alpha subunits to form a native complex
in the brain and heart and regulate the expression and gating properties of Kv4
K(+) channels, but the mechanisms underlying these processes are unknown. Here
we report a co-crystal structure of the complex of human Kv4.3 N-terminus and
KChIP1 at a 3.2-A resolution. The structure reveals a unique clamping action of
the complex, in which a single KChIP1 molecule, as a monomer, laterally clamps
two neighboring Kv4.3 N-termini in a 4:4 manner, forming an octamer. The
proximal N-terminal peptide of Kv4.3 is sequestered by its binding to an
elongated groove on the surface of KChIP1, which is indispensable for the
modulation of Kv4.3 by KChIP1, and the same KChIP1 molecule binds to an adjacent
T1 domain to stabilize the tetrameric Kv4.3 channels. Taken together with
biochemical and functional data, our findings provide a structural basis for the
modulation of Kv4 by KChIPs.
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Figure 1.
Figure 1. The overall architecture of the KChIP1–Kv4.3N
complex. All panels have the same color codes, with some
secondary structural elements labeled specifically. (a)
Schematic representation of the complex structure in one
asymmetric unit. Two KChIP1 and two Kv4.3 molecules are shown in
orange and blue, respectively. (b) The 4:4 complex of
KChIP1-Kv4.3N shown was generated from the complex in a through
symmetric operations. The complex in this panel has the same
size as the one shown in Figure 6a. (c) One KChIP1 molecule
interacts simultaneously with two Kv4.3Ns. In the complex, each
KChIP1 molecule not only binds to the N-terminal peptide of one
Kv4.3 but also interacts with an adjacent Kv4.3 T1 domain,
forming two contact interfaces; the first interface is shown in
the red frame and second interface is shown in the blue frame.
(d) A cartoon of the KChIP1-Kv4.3N complex in 4:4 showing the
clamping effect of KChIP1 molecule on the tetramer of Kv4.3.
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Figure 6.
Figure 6. Comparison of the modeled Kv4.3-KChIP1 channel complex
with Kv1.2-Kv  2.
(a) Side views of Kv1.2–Kv4.3 T1-KChIP complex in which the
Kv4.3 T1 domain fused with transmembrane-spanning domains of
Kv1.2 (left) and Kv1.2-Kv  2
complex (right). The tetrameric subunits of Kv1.2 channels are
labeled in cyan, yellow, pink and green, respectively. KChIP1
and Kv 2
are labeled in blue and wheat, respectively. (b) Top views of a,
showing KChIPs positioned between two adjacent T1 domains (left)
and Kv 2
beneath the T1 domains (right).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Neurosci
(2007,
10,
32-39)
copyright 2007.
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