Modeling the complex of c-Src bound to integrin β3. (A) The complex of c-Src:β3. The integrin β3 is modeled into the inactive c-Src based on the crystal structure of SH3:RGT. The cytoplasmic membrane is shown with bilayers. Activated integrin β3 (black) complexed with its nascent α subunit (orange) is shown as a diagram. The inactive c-Src kinase is shown as a diagram together with a transparent surface. Different functional domains, such as the SH3 domain, SH2 domain, SH2-kinase linker, kinase domain, and the C-terminal tail with phosphorylated Tyr527, are colored by green, yellow, red, blue, and cyan, respectively. The N-terminal membrane-anchoring sequence, designated as c-Src_1-81, is represented by a dashed line. (B) The enlarged view of the putative binding site of c-Src:β3. The RGT peptide and its adjacent Trp260 are shown in stick representation. The choices/positions of mutations (ie, SH3G116R and SH3G127R) used in this study are shown by “*” and “■,” respectively. (C) Structure-based functional characterization of c-Src:β3 by in vitro c-Src activity assays. The YRGT peptide was used to activate c-Src in the presence of SH3, SH3G116R, or SH3G127R. In the controlled experiment, no recombinant SH3 protein was included in the reaction mixture. Values are mean ± SE; n = 3. *P < .05, statistically significant compared with control experiment. **P < .01, statistically significant compared with control experiment.