Figure 8.

VCAM-1 docked to α₄β₇. (A) VCAM-1 domains 1 and 2 (PDB accession no. 1VCA; Jones et al., 1995) were manually placed in an approximate binding orientation to the α₄β₇ head (β-propeller and βI domain only, no Fab). The orientation was optimized by RosettaDock (Lyskov and Gray, 2008). The α₄β₇ headpiece/Act-1 Fab/RO0505376 structure was superimposed, and the pose of VCAM-1 was slightly adjusted to align the putative MIDAS-coordinating carboxyl group in VCAM-1 to that in RO0505376. (B) Zoomed-in view of ligand-binding site in A. (C) A representative class average of MAdCAM-1 bound to the α₄β₇ headpiece from Fig. 7 H. Note the similar orientations between the docked VCAM-1 in the model and MAdCAM-1 bound to α₄β₇. The only difference is that the headpiece is closed in the crystal structure and in an intermediate conformation when bound to MAdCAM-1.