2iim
From Proteopedia
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|PDB= 2iim |SIZE=350|CAPTION= <scene name='initialview01'>2iim</scene>, resolution 1.0Å | |PDB= 2iim |SIZE=350|CAPTION= <scene name='initialview01'>2iim</scene>, resolution 1.0Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= LCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= LCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1lck|1LCK]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2iim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iim OCA], [http://www.ebi.ac.uk/pdbsum/2iim PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2iim RCSB]</span> | ||
}} | }} | ||
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[[Category: Muller, Y A.]] | [[Category: Muller, Y A.]] | ||
[[Category: Romir, J.]] | [[Category: Romir, J.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: PG4]] | ||
| - | [[Category: ZN]] | ||
[[Category: beta-barrel]] | [[Category: beta-barrel]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:44:53 2008'' |
Revision as of 00:44, 31 March 2008
| |||||||
| , resolution 1.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | LCK (Homo sapiens) | ||||||
| Related: | 1LCK
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
SH3 Domain of Human Lck
Contents |
Overview
In cytosolic Src-type tyrosine kinases the Src-type homology 3 (SH3) domain binds to an internal proline-rich motif and the presence or the absence of this interaction modulates the kinase enzymatic activity. The Src-type kinase Lck plays an important role during T-cell activation and development, since it phosphorylates the T-cell antigen receptor in an early step of the activation pathway. We have determined the crystal structure of the SH3 domain from Lck kinase at a near-atomic resolution of 1.0 A. Unexpectedly, the Lck-SH3 domain forms a symmetrical homodimer in the crystal and the dimer comprises two identical zinc-binding sites in the interface. The atomic interactions formed across the dimer interface resemble strikingly those observed between SH3 domains and their canonical proline-rich ligands, since almost identical residues participate in both contacts. Ultracentrifugation experiments confirm that in the presence of zinc ions, the Lck-SH3 domain also forms dimers in solution. The Zn(2+) dissociation constant from the Lck-SH3 dimer is estimated to be lower than 100 nM. Moreover, upon addition of a proline-rich peptide with a sequence corresponding to the recognition segment of the herpesviral regulatory protein Tip, competition between zinc-induced homodimerization and binding of the peptide can be detected by both fluorescence spectroscopy and analytical ultracentrifugation. These results suggest that in vivo, too, competition between Lck-SH3 homodimerization and binding of regulatory proline-rich sequence motifs possibly represents a novel mechanism by which kinase activity is modulated. Because the residues that form the zinc-binding site are highly conserved among Lck orthologues but not in other Src-type kinases, the mechanism might be peculiar to Lck and to its role in the initial steps of T-cell activation.
Disease
Known disease associated with this structure: SCID due to LCK deficiency OMIM:[153390]
About this Structure
2IIM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure analysis and solution studies of human Lck-SH3; zinc-induced homodimerization competes with the binding of proline-rich motifs., Romir J, Lilie H, Egerer-Sieber C, Bauer F, Sticht H, Muller YA, J Mol Biol. 2007 Feb 2;365(5):1417-28. Epub 2006 Oct 21. PMID:17118402
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