9IPC

Poly-alanine model for LH-type bispecific diabody Ex3 composed of 528 and OKT3 Fvs in ternary complex with sEGFR and CD3gamma-epsilon (closed conformation)

9IPC の概要

• エントリーDOI: 10.2210/pdb9ipc/pdb
• EMDBエントリー: 60769
• 分子名称: Epidermal growth factor receptor, LH-type bispecific diabody Ex3, T-cell surface glycoprotein CD3 gamma chain,T-cell surface glycoprotein CD3 epsilon chain (3 entities in total)
• 機能のキーワード: bispecific antibody, diabody, egfr, cd3, ternary complex, lh, ex3, 528, okt3, antitumor protein, antitumor protein-immune system complex, antitumor protein/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 148477.45

構造登録者

Sato, K.,Uehara, S.,Tsugita, A.,Matsui, T.,Asano, R.,Makabe, K.,Yokoyama, T.,Tanaka, Y. (登録日: 2024-07-10, 公開日: 2025-05-28, 最終更新日: 2025-08-06)

主引用文献

Sato, K.,Uehara, S.,Tsugita, A.,Ishii, M.,Ishiyama, S.,Maejima, A.,Nakahara, I.,Nazuka, M.,Matsui, T.,Christos, G.,Yokoyama, T.,Kumagai, I.,Makabe, K.,Asano, R.,Tanaka, Y.
Bispecific antibody-antigen complex structures reveal activity enhancement by domain rearrangement.
Cell Rep, 44:115965-115965, 2025

PubMed Abstract: Bispecific antibodies (BsAbs) have been developed as anti-cancer drugs that accumulate activated T cells on cancer cells by bridging the antigens present in each cell. Ex3 is a diabody-type BsAb composed of an anti-epidermal growth factor receptor (EGFR) antibody and an anti-CD3 antibody. In the design of Ex3, the LH-type domain order (Ex3LH) is shown to have more than 100-fold greater anti-cancer activity than the HL-type domain order (Ex3HL). To understand this phenomenon of activity enhancement by domain-order rearrangement, we report here cryoelectron microscopy (cryo-EM) structures of both Ex3HL and Ex3LH in complex with EGFR and CD3. A structural comparison of the HL and LH types reveals that the domain rearrangement leads to drastic structural changes and that the avoidance of steric hindrance by a favorable bridging angle on the cell surface is the fundamental mechanism for this activity enhancement.

PubMed: 40664209
DOI: 10.1016/j.celrep.2025.115965

実験手法

ELECTRON MICROSCOPY (3.4 Å)