Leukocyte integrin αLβ2 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 alpha(L)beta(2)) reveal how the alpha I domain interacts with its platform formed by the alpha-subunit beta-propeller and beta-subunit beta I domains. The alpha(L)beta(2) structures compared with alpha(X)beta(2) structures show that the aI domain, tethered through its N-linker and a disulfide to a stable beta-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 alpha(L) and alpha(X) subunits. Rerefined beta(2) integrin structures reveal details including pyroglutamic acid at the beta(2) N terminus and bending within the EGF1 domain. Allostery is relayed to the alpha I domain by an internal ligand that binds to a pocket at the interface between the alpha-propeller and beta I domains. Marked differences between the alpha(L) and beta(X) subunit beta-propeller domains concentrate near the binding pocket and aI domain interfaces. Remarkably, movement in allostery in the beta I domain of specificity determining loop 1 (SDL1) causes concerted movement of SDL2 and thereby tightens the binding pocket for the internal ligand.