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PDBsum entry 1vyv
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Transport protein
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PDB id
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1vyv
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Contents |
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* Residue conservation analysis
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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 of the alpha1-Beta subunit interaction of voltage-Gated ca2+ channels.
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Authors
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Y.H.Chen,
M.H.Li,
Y.Zhang,
L.L.He,
Y.Yamada,
A.Fitzmaurice,
Y.Shen,
H.Zhang,
L.Tong,
J.Yang.
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Ref.
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Nature, 2004,
429,
675-680.
[DOI no: ]
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PubMed id
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Abstract
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High-voltage-activated Ca2+ channels are essential for diverse biological
processes. They are composed of four or five subunits, including alpha1,
alpha2-delta, beta and gamma (ref. 1). Their expression and function are
critically dependent on the beta-subunit, which transports alpha1 to the surface
membrane and regulates diverse channel properties. It is believed that the
beta-subunit interacts with alpha1 primarily through the beta-interaction domain
(BID), which binds directly to the alpha-interaction domain (AID) of alpha1;
however, the molecular mechanism of the alpha1-beta interaction is largely
unclear. Here we report the crystal structures of the conserved core region of
beta3, alone and in complex with AID, and of beta4 alone. The structures show
that the beta-subunit core contains two interacting domains: a Src homology 3
(SH3) domain and a guanylate kinase (GK) domain. The AID binds to a hydrophobic
groove in the GK domain through extensive interactions, conferring extremely
high affinity between alpha1 and beta-subunits. The BID is essential both for
the structural integrity of and for bridging the SH3 and GK domains, but it does
not participate directly in binding alpha1. The presence of multiple
protein-interacting modules in the beta-subunit opens a new dimension to its
function as a multi-functional protein.
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Figure 2.
Figure 2: Crystal structure of the beta- [3]
core in complex with its alpha- [1]
binding partner (AID). The  [3]
core can be divided into three regions: an SH3 domain (residues
60 -120 and 170 -175, gold), a HOOK region (residues 121 -169,
purple) and a GK domain (residues 176 -360, green). Residues 226
-244 (forming the  4
helix) are disordered in this molecule but are well resolved in
another one in the same asymmetric unit. Residues 422 -446 of
Ca[V]1.2c containing the entire AID are coloured in orange. This
and all subsequent ribbon diagrams were generated with the
program RIBBONS28.
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Figure 4.
Figure 4: Structural comparisons of the beta--subunit
core. a, Superposition of the apo- [3]
core (red) and [3]
core -AID complex (black). This and all subsequent trace
diagrams were produced with the program Molscript30. b, Close-up
of the AID-binding site of apo- [3]
core (magenta) and [3]
core -AID complex (green). c, Superposition of [3]
core (red) and [4]
core (black). In a and c, only the GK domains were superimposed.
Stereo views of a and c are in Supplementary Fig. 1.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2004,
429,
675-680)
copyright 2004.
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