TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Buchholz, Ina
A1  - McDonnell, Thomas
A1  - Nestler, Peter
A1  - Tharad, Sudarat
A1  - Kulke, Martin
A1  - Radziszewska, Anna
A1  - Ripoll, Vera M.
A1  - Schmidt, Frank
A1  - Hammer, Elke
A1  - Toca‑Herrera, Jose L.
A1  - Rahman, Anisur
A1  - Delcea, Mihaela
T1  - Specific domain V reduction of beta‑2‑glycoprotein I induces protein flexibility and alters pathogenic antibody binding
JF  - Scientific Reports
N2  - Beta-2-glycoprotein I (β2GPI) is a blood protein and the major antigen in the autoimmune disorder
antiphospholipid syndrome (APS). β2GPI exists mainly in closed or open conformations and
comprises of 11 disulfides distributed across five domains. The terminal Cys288/Cys326 disulfide
bond at domain V has been associated with different cysteine redox states. The role of this disulfide
bond in conformational dynamics of this protein has not been investigated so far. Here, we report
on the enzymatic driven reduction by thioredoxin-1 (recycled by Tris(2-carboxyethyl)phosphine;
TCEP) of β2GPI. Specific reduction was demonstrated by Western blot and mass spectrometry
analyses confirming majority targeting to the fifth domain of β2GPI. Atomic force microscopy images
suggested that reduced β2GPI shows a slightly higher proportion of open conformation and is more
flexible compared to the untreated protein as confirmed by modelling studies. We have determined a
strong increase in the binding of pathogenic APS autoantibodies to reduced β2GPI as demonstrated
by ELISA. Our study is relevant for understanding the effect of β2GPI reduction on the protein
structure and its implications for antibody binding in APS patients.
Y1  - 2021
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-43514
SN  - 2045-2322
SS  - 2045-2322
U6  - https://doi.org/10.1038/s41598-021-84021-2
DO  - https://doi.org/10.1038/s41598-021-84021-2
VL  - 11
SP  - 4542
PB  - Springer Nature
ER  -