1q3p
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Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization
OverviewOverview
The Shank/proline-rich synapse-associated protein family of multidomain, proteins is known to play an important role in the organization of, synaptic multiprotein complexes. For instance, the Shank PDZ domain binds, to the C termini of guanylate kinase-associated proteins, which in turn, interact with the guanylate kinase domain of postsynaptic density-95, scaffolding proteins. Here we describe the crystal structures of Shank1, PDZ in its peptide free form and in complex with the C-terminal, hexapeptide (EAQTRL) of guanylate kinase-associated protein (GKAP1a), determined at 1.8- and 2.25-A resolutions, respectively. The structure, shows the typical class I PDZ interaction of PDZ-peptide complex with the, consensus sequence -X-(Thr/Ser)-X-Leu. In addition, Asp-634 within the, Shank1 PDZ domain recognizes the positively charged Arg at -1 position and, hydrogen bonds, and salt bridges between Arg-607 and the side chains of, the ligand at -3 and -5 positions contribute further to the recognition of, the peptide ligand. Remarkably, whether free or complexed, Shank1 PDZ, domains form dimers with a conserved beta B/beta C loop and N-terminal, beta A strands, suggesting a novel model of PDZ-PDZ homodimerization. This, implies that antiparallel dimerization through the N-terminal beta A, strands could be a common configuration among PDZ dimers. Within the, dimeric structure, the two-peptide binding sites are arranged so that the, N termini of the bound peptide ligands are in close proximity and oriented, toward the 2-fold axis of the dimer. This configuration may provide a, means of facilitating dimeric organization of PDZ-target assemblies.
About this StructureAbout this Structure
1Q3P is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization., Im YJ, Lee JH, Park SH, Park SJ, Rho SH, Kang GB, Kim E, Eom SH, J Biol Chem. 2003 Nov 28;278(48):48099-104. Epub 2003 Sep 3. PMID:12954649
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