7NER

Crystal structure of the v-Src SH3 domain Q128R mutant

7NER の概要

• エントリーDOI: 10.2210/pdb7ner/pdb
• 分子名称: v-Src SH3 domain, TETRAETHYLENE GLYCOL, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: beta barrel, sh3 domain, protein binding
• 由来する生物種: Gallus gallus (Chicken)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7151.78

構造登録者

Camara-Artigas, A.,Salinas-Garcia, M.C. (登録日: 2021-02-04, 公開日: 2021-06-02, 最終更新日: 2024-01-31)

主引用文献

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

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: 34076598
DOI: 10.1107/S2059798321004344

実験手法

X-RAY DIFFRACTION (1.55 Å)