1v1t: Difference between revisions
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==Overview== | ==Overview== | ||
PDZ domains are among the most abundant protein modules in the known | 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== | ||
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[[Category: Cooper, D.]] | [[Category: Cooper, D.]] | ||
[[Category: Derewenda, U.]] | [[Category: Derewenda, U.]] | ||
[[Category: Derewenda, Z | [[Category: Derewenda, Z S.]] | ||
[[Category: Devedjiev, Y.]] | [[Category: Devedjiev, Y.]] | ||
[[Category: Grembecka, J.]] | [[Category: Grembecka, J.]] | ||
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[[Category: scaffolding protein]] | [[Category: scaffolding protein]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:30:39 2008'' | ||
Revision as of 16:30, 21 February 2008
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CRYSTAL STRUCTURE OF THE PDZ TANDEM OF HUMAN SYNTENIN IN COMPLEX WITH TNEYKV PEPTIDE
OverviewOverview
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 StructureAbout this Structure
1V1T is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
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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