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PDBsum entry 1x8s
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References listed in PDB file
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Key reference
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Title
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Internal recognition through pdz domain plasticity in the par-6-Pals1 complex.
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Authors
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R.R.Penkert,
H.M.Divittorio,
K.E.Prehoda.
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Ref.
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Nat Struct Mol Biol, 2004,
11,
1122-1127.
[DOI no: ]
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PubMed id
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Abstract
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PDZ protein interaction domains are typically selective for C-terminal ligands,
but non-C-terminal, 'internal' ligands have also been identified. The PDZ domain
from the cell polarity protein Par-6 binds C-terminal ligands and an internal
sequence from the protein Pals1/Stardust. The structure of the Pals1-Par-6 PDZ
complex reveals that the PDZ ligand-binding site is deformed to allow for
internal binding. Whereas binding of the Rho GTPase Cdc42 to a CRIB domain
adjacent to the Par-6 PDZ regulates binding of C-terminal ligands, the
conformational change that occurs upon binding of Pals1 renders its binding
independent of Cdc42. These results suggest a mechanism by which the requirement
for a C terminus can be readily bypassed by PDZ ligands and reveal a complex set
of cooperative and competitive interactions in Par-6 that are likely to be
important for cell polarity regulation.
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Figure 3.
Figure 3. Critical interactions in Pals1 internal PDZ binding.
(a) Par-6 PDZ -C-terminal ligand interactions. The
peptide-binding pocket from the C-terminal peptide -Par-6 PDZ
complex (PDB entry 1RZX) is shown. Peptide residues are labeled
by amino acid and PDZ domain residues are labeled by amino acid
and sequence number. The distance between the C terminus and
Lys165 is shown (solid line) along with interactions between the
carboxylate and the PDZ backbone (dashed lines). (b) Par-6 PDZ
-Pals1 internal ligand interactions. The interactions between
the PDZ domain and peptide are shown as in a.
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Figure 5.
Figure 5. Modes of PDZ C-terminal and internal recognition.
In PDZ C-terminal ligand recognition, the carboxylate-binding
loop enforces C-terminal binding by preventing extension past
the P(0) residue. In the  -finger
internal PDZ recognition mode of recognition, used by
nNOS-syntrophin7 and presumably disulfide-containing ligands8, a
sharp turn in the ligand allows it to bypass the steric
requirement imposed by the carboxylate-binding loop. The Pals1
-Par-6 PDZ interaction represents a new type of internal
interaction in which the carboxylate-binding loop is deformed to
allow for extension past the P(0) residue. An interaction with
the P(+1) residue is critical for this mode of recognition.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2004,
11,
1122-1127)
copyright 2004.
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