4HXJ

Crystal structure of SH3:RGT complex

Summary for 4HXJ

• Entry DOI: 10.2210/pdb4hxj/pdb
• Related: 1FMK
• Descriptor: Proto-oncogene tyrosine-protein kinase Src, C-terminal 3-mer peptide from Integrin beta-3 (3 entities in total)
• Functional Keywords: integrin beta-3, c-src kinase, sh3 domain, rgt, thrombosis, cell signaling, blood clotting, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane: P12931; Cell membrane; Single-pass type I membrane protein: P05106
• Total number of polymer chains: 3
• Total formula weight: 13779.83

Authors

Xiao, R.,Meng, G. (deposition date: 2012-11-11, release date: 2012-11-28, Last modification date: 2023-11-08)

Primary citation

Xiao, R.,Xi, X.D.,Chen, Z.,Chen, S.J.,Meng, G.
Structural framework of c-Src activation by integrin beta 3
Blood, 121:700-706, 2013

PubMed Abstract: The integrin β3-mediated c-Src priming and activation, via the SH3 domain, is consistently associated with diseases, such as the formation of thrombosis and the migration of tumor cells. Conventionally, activation of c-Src is often induced by the binding of proline-rich sequences to its SH3 domain. Instead, integrin β3 uses R(760)GT(762) for priming and activation. Because of the lack of structural information, it is not clear where RGT will bind to SH3, and under what mechanism this interaction can prime/activate c-Src. In this study, we present a 2.0-Å x-ray crystal structure in which SH3 is complexed with the RGT peptide. The binding site lies in the "N"-Src loop of the SH3 domain. Structure-based site-directed mutagenesis showed that perturbation on the "N"-Src loop disrupts the interaction between the SH3 domain and the RGT peptide. Furthermore, the simulated c-Src:β3 complex based on the crystal structure of SH3:RGT suggests that the binding of the RGT peptide might disrupt the intramolecular interaction between the SH3 and linker domains, leading to the disengagement of Trp260:"C"-helix and further activation of c-Src.

PubMed: 23169783
DOI: 10.1182/blood-2012-07-440644

Experimental method

X-RAY DIFFRACTION (2 Å)