Structure, Dynamics and Binding Characteristics of the
Second PDZ Domain of PTP-BL
The PDZ domains of the protein tyrosine phosphatase
PTP-BL mediate interactions by binding to specific amino
acid sequences in target proteins. The solution structure
of the second PDZ domain of PTP-BL, PDZ2, displays a
compact fold with six b strands and two a-helices. A unique
feature of this domain compared to the canonical PDZ fold
is an extended flexible loop at the base of the binding
pocket, termed L1, that folds back onto the protein
backbone, a feature that is shared by both the murine and
human orthologues. The structure of PDZ2 differs
significantly from the orthologous human structure. A
comparison of structural quality indicators clearly
demonstrates that the PDZ2 ensemble is statistically more
reasonable than that of the human orthologue. The analysis
of 15N relaxation data for PDZ2 shows a normal pattern,
with more rigid secondary structures and more flexible loop
structures. Close to the binding pocket, Leu85 and Thr88
display greater mobility when compared to surrounding
residues. Peptide binding studies demonstrated a lack of
interaction between murine PDZ2 and the C terminus of the
murine Fas/ CD95 receptor, suggesting that the Fas/CD95
receptor is not an in vivo target for PDZ2. In addition,
PDZ2 specifically binds the C termini of both human
Fas/CD95 receptor and the RIL protein, despite RIL
containing a non-canonical PDZ-interacting sequence of
E-x-V. A model of PDZ2 with the RIL peptide reveals that
the PDZ2 binding pocket is able to accommodate the bulkier
side-chain of glutamic acid while maintaining crucial
protein to peptide hydrogen bond interactions.
PDB code 1GM1. (
Download)
■ Walma, T., Spronk, C.A.E.M., Tessari, M., Aelen,
J.M.A., Schepens, J., Hendriks, W. & Vuister, G.W.
(2002) “Structure, Dynamics and Binding
Characteristics of the Second PDZ Domain of PTP-BL”,
J. Mol. Biol. 316, 1101-1110.
