Figure 2
Activation of α5β1 integrins in MD simulations compared to activation of αIIbβ3 integrin in crystal structures. (a) Structural overlay of the βA domain (transparent: starting structure; opaque: closest-to-average structure from the last 100 ns) by fitting on the β-propeller domain5. Pink arrows denote the positional shift of the βA domain relative to the β-propeller domain, resulting in an increased propeller-βA domain distance. (b) Overlay of the closed (lighter colors; PDB ID 3FCS) and open (darker colors; PDB ID 3FCU) conformations of the βA domain in αIIbβ3 integrins. Straightening of the α1 helix (orange) and tilting of the α7 helix (blue) are indicated by white arcs and bars. (c) Average of the α1 kink angle (yellow), α7 tilt angle (blue), and β-propeller – βA-domain distance (magenta) over three replicates of MD simulations versus the rank of the bile acids according to their agonist activity towards α5β1 integrin as observed in Fig. 3A-D and ref. 5. Dashed lines represent correlation lines; fit parameters are given in the figures. Vertical lines separate the dataset into inactive (left), weakly active (middle), and highly active (right) bile acids.
