Beta2-Glycoprotein I Binds Thrombin via Exosite I and Exosite II

Authors

Soheila Rahgozar, University of New South Wales
Qiuxia Yang, University of New South Wales
Bill Giannakopoulos, University of New South Wales
Xiaokai Yan, University of New South Wales
Spyridon Miyakis, University of WollongongFollow
S A. Krilis, St. George Hospital, Sydney

RIS ID

74495

Publication Details

Rahgozar, S., Yang, Q., Giannakopoulos, B., Yan, X., Miyakis, S. & Krilis, S. A. (2007). Beta2-Glycoprotein I Binds Thrombin via Exosite I and Exosite II. Arthritis and Rheumatism, 56 (2), 605-613.

Abstract

Objective. Beta2-glycoprotein I (B2GPI) is a dominant antigenic target in antiphospholipid syndrome (APS). Beta2-glycoprotein I may bind to factor XI and serve a physiologic function as a regulator of factor XI activation by thrombin. We undertook this study to investigate the possible interactions of B2GPI with thrombin in B2GPI-regulated factor XI activation by thrombin and to evaluate the effect of anti-B2GPI antibodies on this system. Methods. The B2GPI interaction with thrombin was investigated in direct and competitive assays using B2GPI domain mutants and thrombin-binding exosite oligonucleotides. Beta2-glycoprotein I inhibition of thrombin-mediated factor XI activation was assessed in the presence of 8 anti-B2GPI monoclonal antibodies (mAb) directed against domain I. Results. Domain V of B2GPI was involved in direct binding to thrombin, and exosite I and exosite II on thrombin took part in this interaction. Anti-B2GPI mAb produced a >70% inhibition of thrombin-mediated factor XI activation in the presence of B2GPI.