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PDBsum entry 1u37
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Protein transport
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PDB id
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1u37
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References listed in PDB file
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Key reference
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Title
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Autoinhibition of X11/mint scaffold proteins revealed by the closed conformation of the pdz tandem.
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Authors
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J.F.Long,
W.Feng,
R.Wang,
L.N.Chan,
F.C.Ip,
J.Xia,
N.Y.Ip,
M.Zhang.
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Ref.
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Nat Struct Mol Biol, 2005,
12,
722-728.
[DOI no: ]
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PubMed id
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Abstract
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Members of the X11/Mint family of multidomain adaptor proteins are composed of a
divergent N terminus, a conserved PTB domain and a pair of C-terminal PDZ
domains. Many proteins can interact with the PDZ tandem of X11 proteins,
although the mechanism of such interactions is unclear. Here we show that the
highly conserved C-terminal tail of X11alpha folds back and inserts into the
target-binding groove of the first PDZ domain. The binding of this tail occludes
the binding of other target peptides. This autoinhibited conformation of X11
requires that the two PDZ domains and the entire C-terminal tail be covalently
connected to form an integral structural unit. The autoinhibited conformation of
the X11 PDZ tandem provides a mechanistic explanation for the unique
target-binding properties of the protein and hints at potential regulatory
mechanisms for the X11-target interactions.
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Figure 3.
Figure 3. Structures of the X11  PDZ
domains determined by NMR spectroscopy. (a -c) Ribbon
diagrams of representative NMR structures of PDZ1 (a), PDZ1 in
complex with C-peptide (b) and PDZ2 (c). The C-peptide in b is
shown as an explicit atomic model. (d) Comparison of the  B/
 B
groove conformation in PDZ1 (orange) and PDZ2 of PSD-95
(purple). The two PDZ domains were superimposed on each other
using their respective B
strands. The axis of the B
helix in each PDZ domain is indicated by a solid rod at the
center of the helical cylinder. (e) Surface representation of
the PDZ1 -C-peptide complex. PDZ1 is shown as a surface model,
the backbone of the C-peptide is shown as a white worm, and the
side chains of the last two residues of the C-peptide are shown
as explicit atomic models. The hydrophobic residues of the
surface model are shown in yellow, the positively charged
residues in blue, the negatively charged residues in red and the
rest of amino acids in gray.
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Figure 6.
Figure 6. Correlation of the autoinhibited conformation of X11
with
the target-binding property of the protein. The C termini of
presenilin (DQLAFHQFYI) and calcium channel (HHPDQDHWC) were
fused to glutathione S-transferase, respectively. Purified
recombinant GST fusion proteins were used for binding assays
with wild-type (WT) X11 and
its various mutants, including Y836E, Y836F, PDZ1^* (PDZ1
deficient in ligand binding), PDZ2^* (PDZ2 deficient in ligand
binding) and PDZ12^* (PDZ2 with both its ligand binding sites
disrupted). The amount of X11 protein
was detected by immunoblotting with antibody to c-Myc (9E10).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2005,
12,
722-728)
copyright 2005.
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