6vja | pdb_00006vja
Structure of CD20 in complex with rituximab Fab
Structural highlights
Disease[CD20_HUMAN] Defects in MS4A1 are the cause of immunodeficiency common variable type 5 (CVID5) [MIM:613495]; also called antibody deficiency due to CD20 defect. CVID5 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.[1] Function[CD20_HUMAN] This protein may be involved in the regulation of B-cell activation and proliferation. Publication Abstract from PubMedCluster of Differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and auto-immune disorders, but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX crosslinks CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers. Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.,Rouge L, Chiang N, Steffek M, Kugel C, Croll TI, Tam C, Estevez A, Arthur CP, Koth CM, Ciferri C, Kraft E, Payandeh J, Nakamura G, Koerber JT, Rohou A Science. 2020 Feb 20. pii: science.aaz9356. doi: 10.1126/science.aaz9356. PMID:32079680[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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