Table 1.
Data collection and refinement statistics for the Lyn SH3 domain.
Values in parentheses correspond to the highest resolution shell. For data collection, this corresponds to 1.22–1.20 Å resolution. For refinement, this corresponds to 1.26–1.20 Å resolution. Data are >95% complete at 1.45 Å resolution.
Fig 1.
Crystal structure of the Lyn SH3 domain.
A. Ribbons representation of the Lyn SH3 domain highlights the canonical β-barrel. The structure is colored by crystallographic temperature factor. B. 2Fo−Fc electron density map contoured at 2.0 σ and rendered around Y74, W99 and P114. These residues contribute to the binding site for the polyproline motif [36] and are critical for protein-protein interactions.
Fig 2.
Comparison of the Lyn SH3 structures.
A. Overlay of the X-ray structure with the NMR structure. The Lyn SH3 crystal structure is colored in blue and the NMR structures in grey. The RMSD value is 0.93 Å for all Cα atoms. B. Comparison of the crystal structure of the unliganded Lyn SH3 domain with the NMR structure with peptide bound. Top view of the polyproline binding pocket of the X-ray crystal structure of the Lyn SH3 domain. The highlighted residues are in different conformations than observed in the peptide-bound NMR structure. C. Overlay of the unliganded X-ray crystal structure of unliganded SH3 domain (blue) with peptide-bound NMR structure (grey). The peptide is shown in red. Side chain rotations are indicated by arrows.
Fig 3.
Cancer-associated mutations of the Lyn SH3 domain.
A. Mutations of 18 out of the 61 amino acids of the Lyn SH3 domain were identified by genome sequencing of patients with the indicated types of cancer [23–25]. The table separates these mutations into likely-transformative and likely non-transformative, based upon prior computational analysis [58]. B. Locations of the likely transformative cancer-associated mutations are shown in red. Locations of the likely non-transformative substitutions are shown in green.