title: Leukocyte integrin αLβ2 headpiece structures: The αI domain, the pocket for the internal ligand, and concerted movements of its loops.
abstract: 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.
authors.affiliation: Program in Cellular and Molecular Medicine, Children's Hospital Boston, and Departments of Biological Chemistry and Molecular Pharmacology and of Medicine, Harvard Medical School, Boston, MA 02115; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sen
authors.affiliation: Program in Cellular and Molecular Medicine, Children's Hospital Boston, and Departments of Biological Chemistry and Molecular Pharmacology and of Medicine, Harvard Medical School, Boston, MA 02115; Timothy.Springer@childrens.harvard.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1