8YX1

CD40 in complex with Bleselumab Fab

8YX1 の概要

• エントリーDOI: 10.2210/pdb8yx1/pdb
• 分子名称: Bleselumab, heavy chain, Bleselumab, light chain, Tumor necrosis factor receptor superfamily member 5, ... (4 entities in total)
• 機能のキーワード: cd40, dacetuzumab, bleselumab, agonist activity, tumor necrosis factor, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 134944.52

構造登録者

Caaveiro, J.M.M.,Fernandez-Perez, J.,Tsumoto, K. (登録日: 2024-04-01, 公開日: 2024-05-08, 最終更新日: 2024-11-06)

主引用文献

Asano, R.,Nakakido, M.,Perez, J.F.,Ise, T.,Caaveiro, J.M.M.,Nagata, S.,Tsumoto, K.
Crystal structures of human CD40 in complex with monoclonal antibodies dacetuzumab and bleselumab.
Biochem.Biophys.Res.Commun., 714:149969-149969, 2024

PubMed Abstract: CD40 is a member of the tumor necrosis factor receptor superfamily, and it is widely expressed on immune and non-immune cell types. The interaction between CD40 and the CD40 ligand (CD40L) plays an essential function in signaling, and the CD40/CD40L complex works as an immune checkpoint molecule. CD40 has become a therapeutic target, and a variety of agonistic/antagonistic anti-CD40 monoclonal antibodies (mAbs) have been developed. To better understand the mode of action of anti-CD40 mAbs, we determined the X-ray crystal structures of dacetuzumab (agonist) and bleselumab (antagonist) in complex with the extracellular domain of human CD40, respectively. The structure reveals that dacetuzumab binds to CD40 on the top of cysteine-rich domain 1 (CRD1), which is the domain most distant from the cell surface, and it does not compete with CD40L binding. The binding interface of bleselumab spread between CRD2 and CRD1, overlapping with the binding surface of the ligand. Our results offer important insights for future structural and functional studies of CD40 and provide clues to understanding the mechanism of biological response. These data can be applied to developing new strategies for designing antibodies with more therapeutic efficacy.

PubMed: 38657446
DOI: 10.1016/j.bbrc.2024.149969

実験手法

X-RAY DIFFRACTION (2.7 Å)