A closed binding pocket modifies the binding properties
of an alternatively spliced form of the second PDZ domain
of PTP-BL
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 multi-protein
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 five residue insertion abrogates this
binding. The insert causes distinct structural and
dynamical changes in the alternatively spliced PDZ2:
enlarging the L1 loop between b2 and b3, both lengthening
and changing the orientation of the a2 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.
PDB code 1OZI. (
Download)
■ Walma, T., Aelen, J.M.A., Nabuurs, S., van den
Berk, L., Oostendorp, M., Hendriks, W. & Vuister, G.W.
(2004) “A closed binding pocket modifies the binding
properties of an alternatively spliced form of the second
PDZ domain of PTP-BL”,
Structure
12, 10-20.
