1a81
From Proteopedia
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| - | [[Image:1a81.gif|left|200px]] | + | [[Image:1a81.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF THE TANDEM SH2 DOMAIN OF THE SYK KINASE BOUND TO A DUALLY TYROSINE-PHOSPHORYLATED ITAM''' | + | {{Structure |
| + | |PDB= 1a81 |SIZE=350|CAPTION= <scene name='initialview01'>1a81</scene>, resolution 3.0Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] | ||
| + | |GENE= SYK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF THE TANDEM SH2 DOMAIN OF THE SYK KINASE BOUND TO A DUALLY TYROSINE-PHOSPHORYLATED ITAM''' | ||
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==Overview== | ==Overview== | ||
The Syk family of kinases, consisting of ZAP-70 and Syk, play essential roles in a variety of immune and non-immune cells. This family of kinases is characterized by the presence of two adjacent SH2 domains which mediate their localization to the membrane through receptor encoded tyrosine phosphorylated motifs. While these two kinases share many structural and functional features, the more ubiquitous nature of Syk has suggested that this kinase may accommodate a greater variety of motifs to mediate its function. We present the crystal structure of the tandem SH2 domain of Syk complexed with a dually phosphorylated ITAM peptide. The structure was solved by multiple isomorphous replacement at 3.0 A resolution. The asymmetric unit comprises six copies of the liganded protein, revealing a surprising flexibility in the relative orientation of the two SH2 domains. The C-terminal phosphotyrosine-binding site is very different from the equivalent region of ZAP-70, suggesting that in contrast to ZAP-70, the two SH2 domains of Syk can function as independent units. The conformational flexibility and structural independence of the SH2 modules of Syk likely provides the molecular basis for the more ubiquitous involvement of Syk in a variety of signal transduction pathways. | The Syk family of kinases, consisting of ZAP-70 and Syk, play essential roles in a variety of immune and non-immune cells. This family of kinases is characterized by the presence of two adjacent SH2 domains which mediate their localization to the membrane through receptor encoded tyrosine phosphorylated motifs. While these two kinases share many structural and functional features, the more ubiquitous nature of Syk has suggested that this kinase may accommodate a greater variety of motifs to mediate its function. We present the crystal structure of the tandem SH2 domain of Syk complexed with a dually phosphorylated ITAM peptide. The structure was solved by multiple isomorphous replacement at 3.0 A resolution. The asymmetric unit comprises six copies of the liganded protein, revealing a surprising flexibility in the relative orientation of the two SH2 domains. The C-terminal phosphotyrosine-binding site is very different from the equivalent region of ZAP-70, suggesting that in contrast to ZAP-70, the two SH2 domains of Syk can function as independent units. The conformational flexibility and structural independence of the SH2 modules of Syk likely provides the molecular basis for the more ubiquitous involvement of Syk in a variety of signal transduction pathways. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Immunodeficiency due to defect in CD3-epsilon OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=186830 186830]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 1A81 is a [ | + | 1A81 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A81 OCA]. |
==Reference== | ==Reference== | ||
| - | Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide., Futterer K, Wong J, Grucza RA, Chan AC, Waksman G, J Mol Biol. 1998 Aug 21;281(3):523-37. PMID:[http:// | + | Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide., Futterer K, Wong J, Grucza RA, Chan AC, Waksman G, J Mol Biol. 1998 Aug 21;281(3):523-37. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9698567 9698567] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: syk]] | [[Category: syk]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 09:54:17 2008'' |
Revision as of 07:54, 20 March 2008
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| , resolution 3.0Å | |||||||
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| Gene: | SYK (Homo sapiens) | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THE TANDEM SH2 DOMAIN OF THE SYK KINASE BOUND TO A DUALLY TYROSINE-PHOSPHORYLATED ITAM
Overview
The Syk family of kinases, consisting of ZAP-70 and Syk, play essential roles in a variety of immune and non-immune cells. This family of kinases is characterized by the presence of two adjacent SH2 domains which mediate their localization to the membrane through receptor encoded tyrosine phosphorylated motifs. While these two kinases share many structural and functional features, the more ubiquitous nature of Syk has suggested that this kinase may accommodate a greater variety of motifs to mediate its function. We present the crystal structure of the tandem SH2 domain of Syk complexed with a dually phosphorylated ITAM peptide. The structure was solved by multiple isomorphous replacement at 3.0 A resolution. The asymmetric unit comprises six copies of the liganded protein, revealing a surprising flexibility in the relative orientation of the two SH2 domains. The C-terminal phosphotyrosine-binding site is very different from the equivalent region of ZAP-70, suggesting that in contrast to ZAP-70, the two SH2 domains of Syk can function as independent units. The conformational flexibility and structural independence of the SH2 modules of Syk likely provides the molecular basis for the more ubiquitous involvement of Syk in a variety of signal transduction pathways.
About this Structure
1A81 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide., Futterer K, Wong J, Grucza RA, Chan AC, Waksman G, J Mol Biol. 1998 Aug 21;281(3):523-37. PMID:9698567
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