8HLB

Cryo-EM structure of biparatopic antibody Bp109-92 in complex with TNFR2

8HLB の概要

• エントリーDOI: 10.2210/pdb8hlb/pdb
• EMDBエントリー: 34871
• 分子名称: Tumor necrosis factor receptor superfamily member 1B,Maltose/maltodextrin-binding periplasmic protein, TR109 heavy chain, TR109 light chain, ... (5 entities in total)
• 機能のキーワード: tnfr2, biparatopic antibody, antagonist, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 158513.69

構造登録者

Akiba, H.,Fujita, J.,Ise, T.,Nishiyama, K.,Miyata, T.,Kato, T.,Namba, K.,Ohno, H.,Kamada, H.,Nagata, S.,Tsumoto, K. (登録日: 2022-11-29, 公開日: 2023-10-04, 最終更新日: 2024-10-16)

主引用文献

Akiba, H.,Fujita, J.,Ise, T.,Nishiyama, K.,Miyata, T.,Kato, T.,Namba, K.,Ohno, H.,Kamada, H.,Nagata, S.,Tsumoto, K.
Development of a 1:1-binding biparatopic anti-TNFR2 antagonist by reducing signaling activity through epitope selection.
Commun Biol, 6:987-987, 2023

PubMed Abstract: Conventional bivalent antibodies against cell surface receptors often initiate unwanted signal transduction by crosslinking two antigen molecules. Biparatopic antibodies (BpAbs) bind to two different epitopes on the same antigen, thus altering crosslinking ability. In this study, we develop BpAbs against tumor necrosis factor receptor 2 (TNFR2), which is an attractive immune checkpoint target. Using different pairs of antibody variable regions specific to topographically distinct TNFR2 epitopes, we successfully regulate the size of BpAb-TNFR2 immunocomplexes to result in controlled agonistic activities. Our series of results indicate that the relative positions of the two epitopes recognized by the BpAb are critical for controlling its signaling activity. One particular antagonist, Bp109-92, binds TNFR2 in a 1:1 manner without unwanted signal transduction, and its structural basis is determined using cryo-electron microscopy. This antagonist suppresses the proliferation of regulatory T cells expressing TNFR2. Therefore, the BpAb format would be useful in designing specific and distinct antibody functions.

PubMed: 37758868
DOI: 10.1038/s42003-023-05326-8

実験手法

ELECTRON MICROSCOPY (3.63 Å)