6Y90

Structure of full-length CD20 in complex with Rituximab Fab

Summary for 6Y90

• Entry DOI: 10.2210/pdb6y90/pdb
• EMDB information: 10731 10732 10733 10734
• Descriptor: B-lymphocyte antigen CD20, Rituximab Fab Heavy Chain, Rituximab Fab Light Chain, ... (6 entities in total)
• Functional Keywords: cancer immunotherapy, therapeutic antibody, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 139552.17

Authors

Kumar, A.,Reyes, N. (deposition date: 2020-03-06, release date: 2020-08-26)

Primary citation

Kumar, A.,Planchais, C.,Fronzes, R.,Mouquet, H.,Reyes, N.
Binding mechanisms of therapeutic antibodies to human CD20.
Science, 369:793-799, 2020

PubMed Abstract: Monoclonal antibodies (mAbs) targeting human antigen CD20 (cluster of differentiation 20) constitute important immunotherapies for the treatment of B cell malignancies and autoimmune diseases. Type I and II therapeutic mAbs differ in B cell binding properties and cytotoxic effects, reflecting differential interaction mechanisms with CD20. Here we present 3.7- to 4.7-angstrom cryo-electron microscopy structures of full-length CD20 in complexes with prototypical type I rituximab and ofatumumab and type II obinutuzumab. The structures and binding thermodynamics demonstrate that upon binding to CD20, type II mAbs form terminal complexes that preclude recruitment of additional mAbs and complement components, whereas type I complexes act as molecular seeds to increase mAb local concentration for efficient complement activation. Among type I mAbs, ofatumumab complexes display optimal geometry for complement recruitment. The uncovered mechanisms should aid rational design of next-generation immunotherapies targeting CD20.

PubMed: 32792392
DOI: 10.1126/science.abb8008

Experimental method

ELECTRON MICROSCOPY (3.69 Å)