title: β₂-glycoprotein I, the major target in antiphospholipid syndrome, is a special human complement regulator.
abstract: The human plasma protein β(2)-glycoprotein I (β(2)-GPI) is the major target of autoantibodies associated with antiphospholipid syndrome. However, the biologic function of this abundant protein is still unclear. Here we identify β(2)-GPI as a complement regulator. β(2)-GPI circulates in the plasma in an inactive circular form. On surface binding, such as to apoptotic cells, β(2)-GPI changes conformation to an elongated form that acquires C3/C3b binding activities. β(2)-GPI apparently changes conformation of C3, so that the regulator factor H attaches and induces subsequent degradation by the protease factor I. β(2)-GPI also mediates further cleavage of C3/C3b compared with factor H alone. Our data provide important insights into innate immune regulation by plasma protein β(2)-GPI, which may be exploited in the prevention and therapy of autoimmune disease antiphospholipid syndrome.
authors.affiliation: Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gropp
authors.forename: Nadia
authors.initials: N
authors.lastname: Weber
authors.forename: Michael
authors.initials: M
authors.lastname: Reuter
authors.forename: Sven
authors.initials: S
authors.lastname: Micklisch
authors.forename: Isabell
authors.initials: I
authors.lastname: Kopka
authors.forename: Teresia
authors.initials: T
authors.lastname: Hallström
authors.forename: Christine
authors.initials: C
authors.lastname: Skerka
mesh_terms: D016736:Antiphospholipid Syndrome / Q000276:immunology* / Q000503:physiopathology; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology*; D015153:Blotting, Western; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology* / Q000378:metabolism; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D003179:Complement C3b / Q000276:immunology* / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008968:Molecular Conformation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000276:immunology / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D003176:Complement C3; D011994:Recombinant Proteins; D053482:beta 2-Glycoprotein I; D003179:Complement C3b; D017242:Complement Factor H; D050577:Complement C3-C5 Convertases