Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
13 03 2020
13 03 2020
Historique:
received:
29
10
2019
accepted:
06
02
2020
pubmed:
23
2
2020
medline:
10
4
2020
entrez:
22
2
2020
Statut:
ppublish
Résumé
Cluster of differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and autoimmune 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 cross-links 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.
Identifiants
pubmed: 32079680
pii: science.aaz9356
doi: 10.1126/science.aaz9356
doi:
Substances chimiques
Antigens, CD20
0
Immunoglobulin Fab Fragments
0
Rituximab
4F4X42SYQ6
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1224-1230Subventions
Organisme : Wellcome Trust
ID : 209407/Z/17/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.