Figure 1: Insights into activation of FGFR1 from crystal structures and MD simulations. | Scientific Reports

Figure 1: Insights into activation of FGFR1 from crystal structures and MD simulations.

From: Conformational transition of FGFR kinase activation revealed by site-specific unnatural amino acid reporter and single molecule FRET

Figure 1

(a) Crystal structures of non-phosphorylated (pdb: 4UWY) (left) and phosphorylated (pdb: 3GQI) (right) FGFR1 KD are shown as surface representation. The activation loop (A-loop; red) and kinase insert (KI; pink) (bottom views) and the region at the C-terminus (C; green) (top, rotated view) are represented as ribbons. Three tyrosine phosphorylation sites (Y653 and Y654 in the A-loop and Y766 at the C-terminus) are shown in cyan and residues H589 in the KI and L662 in the A-loop are shown in blue. In the non-phosphorylated structure, flexible region at the C-terminus is modeled according to the position in the structure of FGFR1 KD-3P. (b) The free energy surfaces of the non-phosphorylated (left) and phosphorylated (right) FGFR1 KD are shown as a function of the distance from the reference inactive A-loop conformation (CV1) and to the distance from the reference inactive A-loop conformation (CV2). The contour lines are drawn every 1 kcal/mol. Selected predicted conformations from the top panels are linked by arrows to their ribbon representations (bottom panels) depicting the following conformations of FGFR1 KD: inactive (corresponding to crystal structure in 1a, left), semi-active (corresponding to the energy minimum) and active (corresponding to crystal structure in 1a, right and the energy minimum).

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