title: Intact alphaIIbbeta3 integrin is extended after activation as measured by solution X-ray scattering and electron microscopy.
abstract: Integrins are bidirectional signaling molecules on the cell surface that have fundamental roles in regulating cell behavior and contribute to cell migration and adhesion. Understanding of the mechanism of integrin signaling and activation has been advanced with truncated ectodomain preparations; however, the nature of conformational change in the full-length intact integrin molecule remains an active area of research. Here we used small angle x-ray scattering and electron microscopy to study detergent-solubilized, intact platelet integrin α(IIb)β(3). In the resting state, the intact α(IIb)β(3) adopted a compact, bent conformation. Upon activation with Mn(2+), the average integrin extension increased. Further activation by addition of ligand led to stabilization of the extended state and opening of the headpiece. The observed extension and conformational rearrangement upon activation are consistent with the extension and headpiece opening model of integrin activation.
authors.affiliation: Immune Disease Institute, Children's Hospital Boston, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Eng
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Smagghe
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Springer
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D002465:Cell Movement; D003902:Detergents / Q000737:chemistry / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008024:Ligands; D008345:Manganese / Q000737:chemistry; D008823:Micelles; D008854:Microscopy, Electron / Q000379:methods*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011487:Protein Conformation; D012542:Scattering, Radiation; D015398:Signal Transduction; D014965:X-Rays
chemical_list: D003902:Detergents; D008024:Ligands; D008823:Micelles; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D008345:Manganese