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PDBsum entry 3l4f
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Signaling protein/protein binding
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PDB id
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3l4f
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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 asymmetric association of the betapix coiled coil and shank pdz.
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Authors
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Y.J.Im,
G.B.Kang,
J.H.Lee,
K.R.Park,
H.E.Song,
E.Kim,
W.K.Song,
D.Park,
S.H.Eom.
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Ref.
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J Mol Biol, 2010,
397,
457-466.
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PubMed id
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Abstract
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betaPIX (p21-activated kinase interacting exchange factor) and Shank/ProSAP
protein form a complex acting as a protein scaffold that integrates signaling
pathways and regulates postsynaptic structure. Complex formation is mediated by
the C-terminal PDZ binding motif of betaPIX and the Shank PDZ domain. The
coiled-coil (CC) domain upstream of the PDZ binding motif allows multimerization
of betaPIX, which is important for its physiological functions. We have solved
the crystal structure of the betaPIX CC-Shank PDZ complex and determined the
stoichiometry of complex formation. The betaPIX CC forms a 76-A-long parallel CC
trimer. Despite the fact that the betaPIX CC exposes three PDZ binding motifs in
the C-termini, the betaPIX trimer associates with a single Shank PDZ. One of the
C-terminal ends of the CC forms an extensive beta-sheet interaction with the
Shank PDZ, while the other two ends are not involved in ligand binding and form
random coils. The two C-terminal ends of betaPIX have significantly lower
affinity than the first PDZ binding motif due to the steric hindrance in the
C-terminal tails, which results in binding of a single PDZ domain to the betaPIX
trimer. The structure shows canonical class I PDZ binding with a beta-sheet
interaction extending to position -6 of betaPIX. The betaB-betaC loop of Shank
PDZ undergoes a conformational change upon ligand binding to form the beta-sheet
interaction and to accommodate the bulky side chain of Trp -5. This structural
study provides a clear picture of the molecular recognition of the PDZ ligand
and the asymmetric association of betaPIX CC and Shank PDZ.
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