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PDBsum entry 1ozi
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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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A closed binding pocket and global destabilization modify the binding properties of an alternatively spliced form of the second pdz domain of ptp-Bl.
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Authors
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T.Walma,
J.Aelen,
S.B.Nabuurs,
M.Oostendorp,
L.Van den berk,
W.Hendriks,
G.W.Vuister.
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Ref.
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Structure, 2004,
12,
11-20.
[DOI no: ]
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PubMed id
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Abstract
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PTP-BL is a large phosphatase that is implicated in cellular processes as
diverse as cytokinesis, actin-cytoskeletal rearrangement, and apoptosis. Five
PDZ domains mediate its cellular role by binding to the C termini of target
proteins, forming multiprotein complexes. The second PDZ domain (PDZ2) binds to
the C termini of the tumor suppressor protein APC and the LIM domain-containing
protein RIL; however, in one splice variant, PDZ2as, a 5 residue insertion
abrogates this binding. The insert causes distinct structural and dynamical
changes in the alternatively spliced PDZ2: enlarging the L1 loop between beta2
and beta3, both lengthening and changing the orientation of the alpha2 helix,
giving the base of the binding pocket less flexibility to accommodate ligands,
and destabilizing the entire domain. These changes render the binding pocket
incapable of binding C termini, possibly having implications in the functional
role of PTP-BL.
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Figure 1.
Figure 1. Structural Ensemble and Sequence Alignment of
PD22as(A) Structural ensemble of PDZ2as (stereo diagram);
secondary structures are indicated by cyan (b strand) and pink
(a helix).(B) Protection of amides from H/D exchange. Amides are
depicted as spheres; red spheres indicate amides with high
protection factors, orange spheres, those with intermediate
protection factors, and yellow spheres represent amide with low
protection factors. Gray spheres indicate amides with complete
solvent exchange within the experimental dead time of 20 min.(C
and D) Structural superposition of PDZ2as (blue) with PDZ2
(red). The orientation of the a2 helices differ by  vert,
similar 20° (shown as cylinders) while that of the b2 strands
remain the same (shown as arrows).(E) PDZ2as (PDB code 1ozi)
sequentially aligned with GRIP (1m5z), CASK (1kwa), PSD-95
(1bfe), and DglA (1pdr). The alignments were performed on each
domain with a maximal displacement of 7 Å for each pair of C^a
atoms and a global RMS limit of 4 Å. Protein regions that are
structurally similar to PDZ2as are indicated by underlining.
Secondary structures of both PDZ2 and PDZ2as complexes are
colored as in (A). The 5 residue insertion is boxed in gray.
Numbering schemes are given for PDZ2as (blue) and, for
reference, PDZ2 (red).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
11-20)
copyright 2004.
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