Research article published in Nature, Scientific Reports

Researchers from the Institute for Biophysics (Department of Nanobiotechnology) in collaboration with the group of Prof. Mihaela Delcea (University of Greifswald) and Prof. Anisur Rahman (University College London), have studied the effect of β2GPI reduction on the protein structure, and its implications for antibody binding in autoimmune disorder antiphospholipid syndrome patients.

Beta‑2‑glycoprotein I (β2GPI) is a blood protein and the major antigen in the autoimmune disorder antiphospholipid syndrome (APS). β2GPI can exist in closed or open conformations. The C-terminal Domain V is responsible for the binding on cell surfaces, and the Cys288/Cys326 disulfide bond has been associated with different cysteine redox states.

Thus, we have investigated the its enzymatic reduction (by Western blot and mass spectrometry). In addition, Atomic force microscopy showed that reduced β2GPI presented a slightly higher proportion of open conformation being more flexible than the untreated protein (confirmed by modelling studies).

Furthermore, it was found a strong increase in the binding of pathogenic APS autoantibodies to reduced β2GPI, although the flexibility of the molecule should also be taken into account.

The study has significant implications for how these pathogenic antibodies may respond in sites of oxidative stress where β2GPI, although more studies to fully understand the relationship between function and structure of reduced β2GPI are needed.

Read more in: Nature, Scientific Reports 11 (2021) 4542, Specific domain V reduction of beta‑2‑glycoprotein I induces protein flexibility and alters pathogenic antibody binding

A research paper by: I. Buchholz, T. McDonnell, P. Nestler, S. Tharad, M. Kulke, A. Radziszewska, V. M. Ripoll, F. Schmidt, E. Hammer, J. L. Toca‑Herrera, A. Rahman, M. Delcea