1v1t
From Proteopedia
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==Overview== | ==Overview== | ||
| - | 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 .. | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1V1T is a | + | 1V1T 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=1V1T OCA]. |
==Reference== | ==Reference== | ||
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[[Category: scaffolding protein]] | [[Category: scaffolding protein]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:06:38 2007'' |
Revision as of 12:01, 5 November 2007
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CRYSTAL STRUCTURE OF THE PDZ TANDEM OF HUMAN SYNTENIN IN COMPLEX WITH TNEYKV PEPTIDE
Overview
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.
About this Structure
1V1T is a Single protein structure of sequence from Homo sapiens with BEZ as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
The binding of the PDZ tandem of syntenin to target proteins., Grembecka J, Cierpicki T, Devedjiev Y, Derewenda U, Kang BS, Bushweller JH, Derewenda ZS, Biochemistry. 2006 Mar 21;45(11):3674-83. PMID:16533050
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