8K5G
Structure of the SARS-CoV-2 BA.1 RBD with UT28-RD
Summary for 8K5G
| Entry DOI | 10.2210/pdb8k5g/pdb |
| EMDB information | 36905 |
| Descriptor | UT28K-RD Fab Heavy chain, UT28K-RD Fab Light chain, Spike protein S1 (3 entities in total) |
| Functional Keywords | sars-cov-2, antibody, spike protein, structural protein, viral protein-immune system complex, viral protein/immune system |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 3 |
| Total formula weight | 78366.09 |
| Authors | Chen, L.,Kita, S.,Anraku, Y.,Maenaka, K. (deposition date: 2023-07-21, release date: 2023-12-27, Last modification date: 2024-10-09) |
| Primary citation | Ozawa, T.,Ikeda, Y.,Chen, L.,Suzuki, R.,Hoshino, A.,Noguchi, A.,Kita, S.,Anraku, Y.,Igarashi, E.,Saga, Y.,Inasaki, N.,Taminishi, S.,Sasaki, J.,Kirita, Y.,Fukuhara, H.,Maenaka, K.,Hashiguchi, T.,Fukuhara, T.,Hirabayashi, K.,Tani, H.,Kishi, H.,Niimi, H. Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1. Structure, 32:263-272.e7, 2024 Cited by PubMed Abstract: SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (V T28R/N57D), UT28K-RD targeting the mutation site. In vitro and in vivo experiments demonstrated the efficacy of UT28K-RD in neutralizing Omicron BA.1. Although the experimentally determined structure partially differed from the predicted model, our study serves as a successful case of antibody design, wherein the predicted amino acid substitution enhanced the recognition of the previously elusive Omicron BA.1. We anticipate that numerous similar cases will be reported, showcasing the potential of this approach for improving protein-protein interactions. Our findings will contribute to the development of novel therapeutic strategies for highly mutable viruses, such as SARS-CoV-2. PubMed: 38228146DOI: 10.1016/j.str.2023.12.013 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.41 Å) |
Structure validation
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