8SO3

CryoEM structure of a therapeutic antibody (favezelimab) bound to human LAG3

8SO3 の概要

• エントリーDOI: 10.2210/pdb8so3/pdb
• EMDBエントリー: 40646
• 分子名称: Lymphocyte activation gene 3 protein, favezelimab Fab heavy chain, favezelimab Fab light chain, ... (4 entities in total)
• 機能のキーワード: lymphocyte activation gene 3 protein, favezelimab-lag3 complex, cryoem, single particle reconstruction., immunosuppressant
• 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: 222224.08

構造登録者

Mishra, A.K.,Shahid, S.,Karade, S.S.,Mariuzza, R.A. (登録日: 2023-04-28, 公開日: 2023-09-06, 最終更新日: 2024-11-13)

主引用文献

Mishra, A.K.,Shahid, S.,Karade, S.S.,Agnihotri, P.,Kolesnikov, A.,Hasan, S.S.,Mariuzza, R.A.
CryoEM structure of a therapeutic antibody (favezelimab) bound to human LAG3 determined using a bivalent Fab as fiducial marker.
Structure, 31:1149-, 2023

PubMed Abstract: Lymphocyte activation gene 3 protein (LAG3) is an inhibitory receptor that is upregulated on exhausted T cells in tumors. LAG3 is a major target for cancer immunotherapy with many anti-LAG3 antibodies in clinical trials. However, there is no structural information on the epitopes recognized by these antibodies. We determined the single-particle cryoEM structure of a therapeutic antibody (favezelimab) bound to LAG3 to 3.5 Å resolution, revealing that favezelimab targets the LAG3-binding site for MHC class II, its canonical ligand. The small size of the complex between the conventional (monovalent) Fab of favezelimab and LAG3 (∼100 kDa) presented a challenge for cryoEM. Accordingly, we engineered a bivalent version of Fab favezelimab that doubled the size of the Fab-LAG3 complex and conferred a highly identifiable shape to the complex that facilitated particle selection and orientation for image processing. This study establishes bivalent Fabs as new fiducial markers for cryoEM analysis of small proteins.

PubMed: 37619561
DOI: 10.1016/j.str.2023.07.013

実験手法

ELECTRON MICROSCOPY (3.61 Å)