Leukocyte integrin αLß2 headpiece structures: The αI domain, the pocket for the internal ligand, and concerted movements of its loops.

High-resolution crystal structures of the headpiece of lymphocyte function-associated antigen-1 (integrin αLß2) reveal how the αI domain interacts with its platform formed by the α-subunit ß-propeller and ß-subunit ßI domains. The αLß2 structures compared with αXß2 structures show that the αI domain, tethered through its N-linker and a disulfide to a stable ß-ribbon pillar near the center of the platform, can undergo remarkable pivoting and tilting motions that appear buffered by N-glycan decorations that differ between αL and αX subunits. Rerefined ß2 integrin structures reveal details including pyroglutamic acid at the ß2 N terminus and bending within the EGF1 domain. Allostery is relayed to the αI domain by an internal ligand that binds to a pocket at the interface between the ß-propeller and ßI domains. Marked differences between the αL and αX subunit ß-propeller domains concentrate near the binding pocket and αI domain interfaces. Remarkably, movement in allostery in the ßI domain of specificity determining loop 1 (SDL1) causes concerted movement of SDL2 and thereby tightens the binding pocket for the internal ligand.