7NER
Crystal structure of the v-Src SH3 domain Q128R mutant
Summary for 7NER
| Entry DOI | 10.2210/pdb7ner/pdb |
| Descriptor | v-Src SH3 domain, TETRAETHYLENE GLYCOL, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | beta barrel, sh3 domain, protein binding |
| Biological source | Gallus gallus (Chicken) |
| Total number of polymer chains | 1 |
| Total formula weight | 7151.78 |
| Authors | Camara-Artigas, A.,Salinas-Garcia, M.C. (deposition date: 2021-02-04, release date: 2021-06-02, Last modification date: 2024-01-31) |
| Primary citation | Salinas-Garcia, M.C.,Plaza-Garrido, M.,Camara-Artigas, A. The impact of oncogenic mutations of the viral Src kinase on the structure and stability of the SH3 domain. Acta Crystallogr D Struct Biol, 77:854-866, 2021 Cited by PubMed Abstract: Src kinase belongs to the family of Src-related nonreceptor tyrosine kinases. Because of its physiological role in cell growth and proliferation, its activity is strictly controlled by several mechanisms. Nevertheless, in viral Src kinase (v-Src) some of these mechanisms fail, and its uncontrolled activity is responsible for the occurrence of cancer. Here, the crystal structures of three SH3-domain mutants of v-Src were determined to unveil the effects of these oncogenic mutations in this regulatory domain. Mutations in the n-Src and distal loops have a low impact on the overall structure of the domain and its capacity to form intertwined dimers. However, mutations in the RT loop compromise the stability of the domain and make the protein very prone to aggregation. Additionally, these mutations prevent the formation of intertwined dimers. The results show a synergistic effect between mutations in the RT loop and those in the n-Src and distal loops. Analysis of the structures of the v-Src SH3-domain mutants and the closed inactive conformation of cellular Src kinase (c-Src) point to a loss of the interactions that are required to establish the compact inactive form of the kinase. Nevertheless, an analysis of structures of the c-Src SH3 domain complexed with class I and II peptides points to minor changes in the interactions between the v-Src SH3 domain and these peptides. In this way, the structures reported here indicate that mutations in the RT loop might impair the kinase regulation mechanism without affecting the recognition of short proline-rich motifs in the target proteins of the kinase, thus explaining the oncogenic behaviour of the protein. PubMed: 34076598DOI: 10.1107/S2059798321004344 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
Download full validation report
