6Y92

Structure of full-length CD20 in complex with Ofatumumab Fab

6Y92 の概要

• エントリーDOI: 10.2210/pdb6y92/pdb
• EMDBエントリー: 10731 10732 10733 10734
• 分子名称: B-lymphocyte antigen CD20, Ofatumumab Fab light chain, Ofatumumab Fab heavy chain, ... (4 entities in total)
• 機能のキーワード: cancer immunotherapy, therapeutic antibody, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 135376.97

構造登録者

Kumar, A.,Reyes, N. (登録日: 2020-03-06, 公開日: 2020-08-26, 最終更新日: 2025-10-01)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4.73 Å)