Speculative model of the initial tertiary and quaternary changes during occupancy of activated integrins that lack an α-I domain. Ligand binding to the MIDAS motif of the β-I domain (M) triggers conformational changes in the three MIDAS loops (numbered 1–3) that cause a shift of helix α1 and MIDAS loop 3 toward the βF-α7 loop (black arrows) and a loosening of the contacts between the β-I domain and the propeller. These movements cause steric clashes that are relieved by a rotation of the β-I domain around the indicated pivot point (red circle) at the hybrid–β-I domain boundary, separating the β-I from the propeller. Helix α7 remains in position, thus freeing itself from its contacts with MIDAS loop 3 and helix α1. That is, there is a net shift of helix α7 with respect to the β-I domain as observed in the α-I domain. Since occupancy activates integrins (Du et al., 1993), a reversal of the order of these events could account for integrin activation. In support of this idea, three mutations (B) shown previously to block activation (Baker et al., 1997) define a path between the movement of MIDAS loop 3 and helix α7; an activation epitope maps to the base of α1 (labeled H) at the β-I–hybrid interface. Red highlighted loops on the propeller map the location of chimeras that switch ligand recognition specificities between integrin αv and α5 subunits.