4hvw
Crystal structure of the T98E c-Src-SH3 domain mutant in complex with the high affinity peptide VSL12
Structural highlights
FunctionSRC_CHICK Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.[1] [2] Publication Abstract from PubMedThe atomic resolution crystal structures of complexes between the SH3 domain of the c-Src tyrosine kinase and two high-affinity peptides belonging to class I and class II have been solved. The crystals of the Thr98Asp and Thr98Glu mutants in complex with the APP12 peptide (APPLPPRNRPRL) belonged to the trigonal space group P3121 and in both cases the asymmetric unit was composed of one molecule of the SH3-APP12 complex. The crystals of the Thr98Glu mutant in complex with the VSL12 peptide (VSLARRPLPLP) belonged to the trigonal space group P3221 and the asymmetric unit was also composed of a single molecule of the SH3-VSL12 complex. All crystals were obtained in the presence of PEG 300 under the same conditions as reported for the intertwined dimeric structure of the c-Src SH3 domain, but the presence of the peptide stabilizes the monomeric form of the domain. These structures allow a detailed analysis of the role of salt bridges, cation-pi interactions and hydrogen bonds in the binding of proline-rich motifs to the c-Src SH3 domain. Moreover, these crystallographic structures allow the role of water molecules in the binding of these motifs to the c-Src SH3 domain to be studied for the first time. Atomic resolution structures of the c-Src SH3 domain in complex with two high-affinity peptides from classes I and II.,Bacarizo J, Camara-Artigas A Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):756-66. doi:, 10.1107/S0907444913001522. Epub 2013 Apr 11. PMID:23633584[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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