title: Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation.
abstract: The structure of the I domain of integrin alpha L beta 2 bound to the Ig superfamily ligand ICAM-1 reveals the open ligand binding conformation and the first example of an integrin-IgSF interface. The I domain Mg2+ directly coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue Glu-241 enables a critical salt bridge. Liganded and unliganded structures for both high- and intermediate-affinity mutant I domains reveal that ligand binding can induce conformational change in the alpha L I domain and that allosteric signals can convert the closed conformation to intermediate or open conformations without ligand binding. Pulling down on the C-terminal alpha 7 helix with introduced disulfide bonds ratchets the beta 6-alpha 7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity.
authors.affiliation: The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
authors.forename: Motomu
authors.initials: M
authors.lastname: Shimaoka
authors.affiliation: The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
authors.forename: Tsan
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Dana-Farber Cancer Institute, Department of Pediatrics, Department of Medicine, Department of Biological Chemistry, Department of Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Jin-Huan
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Dana-Farber Cancer Institute, Department of Pediatrics, Department of Medicine, Department of Biological Chemistry, Department of Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Dana-Farber Cancer Institute, Department of Pediatrics, Department of Medicine, Department of Biological Chemistry, Department of Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Dong
authors.affiliation: The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
authors.forename: Chang-Duk
authors.initials: CD
authors.lastname: Jun
authors.affiliation: The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
authors.forename: Alison
authors.initials: A
authors.lastname: McCormack
authors.affiliation: Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439.
authors.forename: Rongguang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.affiliation: The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
authors.forename: Junichi
authors.initials: J
authors.lastname: Takagi
authors.affiliation: Dana-Farber Cancer Institute, Department of Pediatrics, Department of Medicine, Department of Biological Chemistry, Department of Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Jia-Huai
authors.initials: JH
authors.lastname: Wang
authors.affiliation: The Center for Blood Research, Department of Pathology, Department of Anesthesia, Department of Pediatrics, Boston, Massachusetts 02115.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D005973:Glutamine / Q000737:chemistry / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013059:Spectrum Analysis, Raman; D020349:Surface Plasmon Resonance
chemical_list: D004220:Disulfides; D016023:Integrins; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D005973:Glutamine; D018799:Intercellular Adhesion Molecule-1; D008274:Magnesium