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-Structure paper
タイトル | CryoEM structure of a therapeutic antibody (favezelimab) bound to human LAG3 determined using a bivalent Fab as fiducial marker. |
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ジャーナル・号・ページ | Structure, Vol. 31, Issue 10, Page 1149-11157.e3, Year 2023 |
掲載日 | 2023年10月5日 |
![]() | Arjun K Mishra / Salman Shahid / Sharanbasappa S Karade / Pragati Agnihotri / Alexander Kolesnikov / S Saif Hasan / Roy A Mariuzza / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 2.1 - 3.61 Å |
構造データ | EMDB-40646, PDB-8so3: EMDB-40716, PDB-8sr0: ![]() PDB-6wkm: ![]() PDB-8fwh: |
化合物 | ![]() ChemComp-HOH: ![]() ChemComp-EDO: ![]() ChemComp-NAG: |
由来 |
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![]() | IMMUNE SYSTEM / Anti Human LAG3 / Fab / inhibitory receptors / IMMUNOSUPPRESSANT / Lymphocyte activation gene 3 protein / favezelimab-LAG3 complex / cryoEM / Single particle reconstruction. |