8BLQ

Cryo-EM structure of the CODV-IL13-RefAb triple complex

8BLQ の概要

• エントリーDOI: 10.2210/pdb8blq/pdb
• EMDBエントリー: 16113
• 分子名称: CODV-Fab, heavy chain, CODV-Fab, light chain, RefAb, light chain, ... (5 entities in total)
• 機能のキーワード: cytosolic, bispecific, fab, therapeutical, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 130972.11

構造登録者

Fernandez-Martinez, D.,Kandiah, E. (登録日: 2022-11-10, 公開日: 2023-06-07, 最終更新日: 2024-11-13)

主引用文献

Fernandez-Martinez, D.,Tully, M.D.,Leonard, G.,Mathieu, M.,Kandiah, E.
Structural insights into the bi-specific cross-over dual variable antibody architecture by cryo-EM.
Sci Rep, 13:8694-8694, 2023

PubMed Abstract: Multi-specific antibodies (msAbs) are being developed as next generation antibody-based therapeutics. Knowledge of the three-dimensional structures, in the full antibody context, of their fragment antigen-binding (Fab) moieties with or without bound antigens is key to elucidating their therapeutic efficiency and stability. However, the flexibility of msAbs, a feature essential for their multi specificity, has hindered efforts in this direction. Cross-Over Dual Variable immunoglobulin (CODV) is a promising bispecific antibody format, designed to simultaneously target the interleukins IL4 and IL13. In this work we present the biophysical and structural characterisation of a CODV:IL13 complex in the full antibody context, using cryo-electron microscopy at an overall resolution of 4.2 Å. Unlike the 1:2 stoichiometry previously observed for CODV:IL4, CODV:IL13 shows a 1:1 stoichiometry. As well as providing details of the IL13-CODV binding interface, including the residues involved in the epitope-paratope region, the structure of CODV:IL13 also validates the use of labelling antibody as a new strategy for the single particle cryo-EM study of msAbs in complex with one, or more, antigens. This strategy reduced the inherent flexibility of the IL13 binding domain of CODV without inducing either structural changes at the epitope level or steric hindrance between the IL4 and IL13 binding regions of CODV. The work presented here thus also contributes to the development of methodology for the structural study of msAbs, a promising platform for cancer immunotherapy.

PubMed: 37248285
DOI: 10.1038/s41598-023-35678-4

実験手法

ELECTRON MICROSCOPY (3.97 Å)