9K3T
Cryo-EM structure of TMPRSS2 in complex with Fab fragments of 752 mAb and 2228 mAb
Summary for 9K3T
| Entry DOI | 10.2210/pdb9k3t/pdb |
| EMDB information | 62028 |
| Descriptor | Transmembrane protease serine 2, Fab 752 light chain, Fab 752 heavy chain, ... (5 entities in total) |
| Functional Keywords | hydrolase, immune system, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 140158.44 |
| Authors | Katsura, K.,Hisano, T.,Matsumoto, T.,Shirouzu, M. (deposition date: 2024-10-20, release date: 2025-10-15, Last modification date: 2025-12-31) |
| Primary citation | Harada, M.,Matsumoto, T.,Yamamoto, M.,Goda, J.,Idei, A.,Ohtaki, K.,Kojima, N.,Yoneda, N.,Miyauchi, K.,Katsura, K.,Ikeda, M.,Hanada, K.,Ishizuka-Katsura, Y.,Hosaka, T.,Hisano, T.,Kaizuka, T.,Yamamoto, T.,Matsuda, M.,Nakayama, M.,Sugimoto-Ishige, A.,Sakuma, M.,Hashimoto, R.,Takayama, K.,Nakayama, M.,Nguyen, C.T.,Ishigaki, H.,Itoh, Y.,Hashizume, Y.,Yoshida, M.,Kawaguchi, Y.,Takeda, M.,Koseki, H.,Shirouzu, M.,Inoue, J.I.,Saito, T. Monoclonal antibodies against human TMPRSS2 prevent infection by any SARS-CoV-2 variant. Iscience, 28:113424-113424, 2025 Cited by PubMed Abstract: The transmembrane serine protease 2 (TMPRSS2) plays a critical role in SARS-CoV-2 infection by priming the viral Spike (S) protein for host cell entry and thus represents a potential target for COVID-19 therapy. Here monoclonal antibodies (mAbs) against human TMPRSS2 were established for therapeutic application. infection by SARS-CoV-2 of cell lines and human lung organoids was strongly inhibited by the TMPRSS2 mAbs. These mAbs inhibited infection of all SARS-CoV-2 variants tested including omicron. mAbs recognized epitopes different from the enzymatic active site and did not inhibit protease activity, suggesting blockade of steric interactions of S protein-ACE2/TMPRSS2. The inhibitory activity of the mAbs was examined in human /-double knock-in mouse and macaque models. Analysis of viral titers and histopathological analysis of the lung in these infected animals indicated that the TMPRSS2 mAb effectively suppressed viral titers and induction of inflammation . PubMed: 41393976DOI: 10.1016/j.isci.2025.113424 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.15 Å) |
Structure validation
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