1w9o: Difference between revisions

PDZ domains are among the most abundant protein modules in the known, genomes. Their main function is to provide scaffolds for, membrane-associated protein complexes by binding to the cytosolic, C-terminal fragments of receptors, channels, and other integral membrane, proteins. Here, using both heteronuclear NMR and single crystal X-ray, diffraction, we show how peptides with different sequences, including, those corresponding to the C-termini of syndecan, neurexin, and ephrin B, can simultaneously bind to both PDZ domains of the scaffolding protein, syntenin. The PDZ2 domain binds these peptides in the canonical fashion, and an induced fit mechanism allows for the accommodation of a range of, side chains in the P(0) and P(-)(2) positions. However, binding to the, PDZ1 domain requires that the target peptide assume a noncanonical, conformation. These data help explain how syntenin, and perhaps other, PDZ-containing proteins, may preferentially bind to dimeric and clustered, targets, and provide a mechanistic explanation for the previously reported, cooperative ligand binding by syntenin's two PDZ domains.

1W9O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with BEZ as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W9O OCA].  

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