7PW2
Crystal structure of the Abl SH3 domain V73E-A74S-S75R-G76T-D77E mutant
Summary for 7PW2
| Entry DOI | 10.2210/pdb7pw2/pdb |
| Descriptor | Non-specific protein-tyrosine kinase (2 entities in total) |
| Functional Keywords | beta barrel, sh3 domain, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 6721.40 |
| Authors | Camara-Artigas, A.,Salinas Garcia, M.C. (deposition date: 2021-10-05, release date: 2022-09-14, Last modification date: 2025-09-10) |
| Primary citation | 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 Cited by 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: 40862305DOI: 10.1107/S2059798325006977 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.1 Å) |
Structure validation
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