| http://purl.uniprot.org/citations/17118402 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17118402 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.jmb.2006.10.058"xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/author | "Egerer-Sieber C."xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/author | "Lilie H."xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/author | "Muller Y.A."xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/author | "Sticht H."xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/author | "Bauer F."xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/author | "Romir J."xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/name | "J Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/pages | "1417-1428"xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/title | "Crystal structure analysis and solution studies of human Lck-SH3; zinc-induced homodimerization competes with the binding of proline-rich motifs."xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://purl.uniprot.org/core/volume | "365"xsd:string |
| http://purl.uniprot.org/citations/17118402 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17118402 |
| http://purl.uniprot.org/citations/17118402 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/17118402 |
| http://purl.uniprot.org/uniprot/P06239#attribution-94A76BC2BA3B0DEB7BD50F797C7E04C9 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/17118402 |
| http://purl.uniprot.org/uniprot/#_P06239-mappedCitation-17118402 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17118402 |
| http://purl.uniprot.org/uniprot/P06239 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/17118402 |