6WKM

Fab Fragment of Anti-human LAG3 antibody (22D2)

Summary for 6WKM

• Entry DOI: 10.2210/pdb6wkm/pdb
• Descriptor: 22D2 Fab Heavy Chain, 22D2 Fab Light Chain (3 entities in total)
• Functional Keywords: anti human lag3, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 2
• Total formula weight: 48977.37

Authors

Agnihotri, P.,Mishra, A.K.,Mariuzza, R.A. (deposition date: 2020-04-16, release date: 2021-04-21, Last modification date: 2024-10-23)

Primary citation

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, 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

Experimental method

X-RAY DIFFRACTION (2.1 Å)