7PVY

Crystal structure of the c-Src SH3 domain E93V-S94A-R95S-T96G mutant

7PVY の概要

• エントリーDOI: 10.2210/pdb7pvy/pdb
• 分子名称: Isoform 2 of Proto-oncogene tyrosine-protein kinase Src (2 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: 6646.21

構造登録者

Camara-Artigas, A.,Salinas Garcia, M.C. (登録日: 2021-10-05, 公開日: 2022-09-14, 最終更新日: 2025-09-10)

主引用文献

Salinas-Garcia, M.C.,Plaza-Garrido, M.,Martinez, J.C.,Camara-Artigas, A.
Understanding domain swapping in the c-Src SH3 domain through hinge-loop mutagenesis.
Acta Crystallogr D Struct Biol, 2025

PubMed Abstract: The c-Src SH3 domain is one of the best-characterized modular domains from a biophysical and structural point of view. This SH3 domain displays noncanonical alternative folding, forming 3D domain-swapped oligomers and amyloid fibrils. These features make this small protein an ideal model for studying these phenomena. Residues in the regions that favour unfolding of the monomer and those in the hinge loop have been deeply studied in proteins undergoing 3D domain swapping. To study the role of these residues in the unfolding of the c-Src SH3 domain, we have constructed several chimeric proteins by interchanging residues in the RT and n-Src loops between the c-Src SH3 and Abl SH3 domains. The RT (the region between β1 and β2) and n-Src (the region between β2 and β3) loops create two sides of the shallow hydrophobic groove where proline-rich motif sequences bind to the SH3 domain. In addition to the structural information, we have performed a biophysical characterization of these chimeric constructs. The c-Src SH3 domain bearing the loops of the Abl SH3 shows minor changes in stability. Interestingly, these replacements do not prevent the formation of domain-swapped dimers. However, the interchange of one or two loops within the Abl SH3 domain produces a noticeable reduction in its stability but does not promote the formation of 3D domain-swapped oligomers. Thus, our results indicate that although the composition of the hinge loop is likely to play a role in the interchange of structural elements to form the intertwined dimers, it is not the sole driving force in their formation.

PubMed: 40862305
DOI: 10.1107/S2059798325006977

実験手法

X-RAY DIFFRACTION (1.4 Å)