3qjm

Structural flexibility of Shank PDZ domain is important for its binding to different ligands

spinqualitylabelsall models 3qjm, resolution 2.31Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qjm is a 4 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3qjn Gene: Shank1 (Buffalo rat) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SHAN1_RAT] Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction. Overexpression promotes maturation of dendritic spines and the enlargement of spine heads via its ability to recruit Homer to postsynaptic sites, and enhances presynaptic function. Publication Abstract from PubMed The PDZ domain of the shank protein interacts with numerous cell membrane receptors and cytosolic proteins via the loosely defined binding motif X-(Ser/Thr)-X-Phi-COOH (Phi represents hydrophobic residues) at the carboxyl terminus of its target protein. This enables shank to serve as a membrane-associated scaffold for the assembly of signaling complexes. As the list of proteins that bind to the shank PDZ domain grows, it is not immediately clear what structural element(s) mediate this domain's target specificity or the plasticity required to bind its different targets. Here, we have determined the crystal structure of the shank1 PDZ in complex with the betaPIX C-terminal pentapeptide (642-646, DETNL) at 2.3A resolution and modeled shank1 PDZ binding to selected pentapeptide ligands. The resulting structures revealed a large hydrophobic pocket within the PDZ domain that can accommodate a variety of ligand residues at the P(0) position. A H-bond between His735 and Ser/Thr at the P(-2) position is invariant throughout the model structures. In addition, we identified multiple PDZ domain residues that are able to form H-bonds and salt bridges with an incoming target protein. Overall, our study provides a new level of understanding of the specificity and structural plasticity of the shank PDZ domain. The structural flexibility of the shank1 PDZ domain is important for its binding to different ligands.,Lee JH, Park H, Park SJ, Kim HJ, Eom SH Biochem Biophys Res Commun. 2011 Apr 1;407(1):207-12. Epub 2011 Mar 3. PMID:21376703 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Shank protein

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