6YXK

Crystal structure of ACPA 3F3 in complex with cit-vimentin 59-74

Summary for 6YXK

• Entry DOI: 10.2210/pdb6yxk/pdb
• Descriptor: ACPA 3F3 Fab fragment - heavy chain, ACPA 3F3 Fab fragment - light chain, Citrullinated Vimentin (59-74), ... (5 entities in total)
• Functional Keywords: anti-citrullinated protein antibody fab fragment, citrullinated vimentin, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 50268.93

Authors

Ge, C.,Holmdahl, R. (deposition date: 2020-05-03, release date: 2021-05-12, Last modification date: 2024-11-20)

Primary citation

Kissel, T.,Ge, C.,Hafkenscheid, L.,Kwekkeboom, J.C.,Slot, L.M.,Cavallari, M.,He, Y.,van Schie, K.A.,Vergroesen, R.D.,Kampstra, A.S.B.,Reijm, S.,Stoeken-Rijsbergen, G.,Koeleman, C.,Voortman, L.M.,Heitman, L.H.,Xu, B.,Pruijn, G.J.M.,Wuhrer, M.,Rispens, T.,Huizinga, T.W.J.,Scherer, H.U.,Reth, M.,Holmdahl, R.,Toes, R.E.M.
Surface Ig variable domain glycosylation affects autoantigen binding and acts as threshold for human autoreactive B cell activation.
Sci Adv, 8:eabm1759-eabm1759, 2022

PubMed Abstract: The hallmark autoantibodies in rheumatoid arthritis are characterized by variable domain glycans (VDGs). Their abundant occurrence results from the selective introduction of N-linked glycosylation sites during somatic hypermutation, and their presence is predictive for disease development. However, the functional consequences of VDGs on autoreactive B cells remain elusive. Combining crystallography, glycobiology, and functional B cell assays allowed us to dissect key characteristics of VDGs on human B cell biology. Crystal structures showed that VDGs are positioned in the vicinity of the antigen-binding pocket, and dynamic modeling combined with binding assays elucidated their impact on binding. We found that VDG-expressing B cell receptors stay longer on the B cell surface and that VDGs enhance B cell activation. These results provide a rationale on how the acquisition of VDGs might contribute to the breach of tolerance of autoreactive B cells in a major human autoimmune disease.

PubMed: 35138894
DOI: 10.1126/sciadv.abm1759

Experimental method

X-RAY DIFFRACTION (2 Å)