High-resolution crystal structures of the headpiece of lymphocyte
function-associated antigen-1 (integrin αLβ2) reveal how the αI domain
interacts with its platform formed by the α-subunit β-propeller and β-subunit
βI domains. The αLβ2 structures compared with αXβ2 structures show that the
αI domain, tethered through its N-linker and a disulfide to a stable β-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 β2 integrin structures reveal details including
pyroglutamic acid at the β2 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 β-propeller and βI domains. Marked
differences between the αL and αX subunit β-propeller domains concentrate
near the binding pocket and αI domain interfaces. Remarkably, movement in
allostery in the βI domain of specificity determining loop 1 (SDL1) causes
concerted movement of SDL2 and thereby tightens the binding pocket for the
internal ligand.
