Intact alphaIIbbeta3 integrin is extended after activation as measured by solution X-ray scattering and electron microscopy.

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  • Author(s): Eng ET;Eng ET; Smagghe BJ; Walz T; Springer TA
  • Source:
    The Journal of biological chemistry [J Biol Chem] 2011 Oct 07; Vol. 286 (40), pp. 35218-26. Date of Electronic Publication: 2011 Aug 09.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Microscopy, Electron/*methods ; Platelet Glycoprotein GPIIb-IIIa Complex/*metabolism; Blood Platelets/metabolism ; Cell Movement ; Detergents/chemistry ; Detergents/pharmacology ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Ligands ; Manganese/chemistry ; Micelles ; Protein Conformation ; Scattering, Radiation ; Signal Transduction ; X-Rays
    • 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.
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    • Grant Information:
      P01 HL103526 United States HL NHLBI NIH HHS; United States HHMI Howard Hughes Medical Institute; HL103526 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Detergents)
      0 (Ligands)
      0 (Micelles)
      0 (Platelet Glycoprotein GPIIb-IIIa Complex)
      42Z2K6ZL8P (Manganese)
    • Publication Date:
      Date Created: 20110812 Date Completed: 20111209 Latest Revision: 20211020
    • Publication Date:
      20221213
    • Accession Number:
      PMC3186426
    • Accession Number:
      10.1074/jbc.M111.275107
    • Accession Number:
      21832081