title: Conformation of beta2glycoprotein I and its effect on coagulation.
abstract: β(2)glycoprotein I (β(2)GPI) is the major antigen in the antiphospholipid syndrome. It has been shown that β(2)GPI can adapt to different conformations, a circular, a S-shaped and a J-shaped conformation. In literature anticoagulant properties of β(2)GPI have been indicated, though there is no consensus on how β(2)GPI exerts a certain action. This article will first review existing data on the conformation of β(2)GPI. In addition, we will investigate whether the conformation of β(2)GPI plays a role in in the proposed anticoagulant activity of β(2)GPI. We investigated the effect of native β(2)GPI and phospholipid-bound β(2)GPI on thrombin generation (TG). Native β(2)GPI was found to have no significant effect on the TG regardless of the concentration of tissue factor. On the contrary, β(2)GPI preincubated with phospholipids significantly inhibited TG triggered with low TF concentration, suggesting an effect on the intrinsic pathway. This indicates that native β(2)GPI in circulation obtains its anticoagulant activity in the presence of anionic phospholipids such as activated blood cells thereby serving as an inhibitory modulator in hemostasis.
authors.affiliation: Synapse BV, Maastricht, The Netherlands.
authors.forename: Marisa
authors.initials: M
authors.lastname: Ninivaggi
authors.forename: Hilde
authors.initials: H
authors.lastname: Kelchtermans
authors.forename: Theo
authors.initials: T
authors.lastname: Lindhout
authors.forename: Bas
authors.initials: B
authors.lastname: de Laat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016736:Antiphospholipid Syndrome / Q000097:blood; D001777:Blood Coagulation; D006801:Humans; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000097:blood; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000097:blood* / Q000737:chemistry
chemical_list: D010743:Phospholipids; D053482:beta 2-Glycoprotein I; D013925:Thromboplastin; D013917:Thrombin