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8SO3

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

Summary for 8SO3
Entry DOI10.2210/pdb8so3/pdb
EMDB information40646
DescriptorLymphocyte activation gene 3 protein, favezelimab Fab heavy chain, favezelimab Fab light chain, ... (4 entities in total)
Functional Keywordslymphocyte activation gene 3 protein, favezelimab-lag3 complex, cryoem, single particle reconstruction., immunosuppressant
Biological sourceHomo sapiens (human)
More
Total number of polymer chains6
Total formula weight222224.08
Authors
Mishra, A.K.,Shahid, S.,Karade, S.S.,Mariuzza, R.A. (deposition date: 2023-04-28, release date: 2023-09-06, Last modification date: 2024-11-13)
Primary citationMishra, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.61 Å)
Structure validation

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