Summary for 6WLA
| Entry DOI | 10.2210/pdb6wla/pdb |
| Descriptor | Fab ch128.1 heavy chain, Fab ch128.1 light chain, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | antibody, anti-hutfr1, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 141144.87 |
| Authors | Helguera, G.,Rodriguez, J.A.,Sawaya, M.,Cascio, D.,Zink, S.,Ziegenbein, J.,Short, C. (deposition date: 2020-04-18, release date: 2021-03-24, Last modification date: 2024-10-16) |
| Primary citation | Hickerson, B.T.,Daniels-Wells, T.R.,Payes, C.,Clark, L.E.,Candelaria, P.V.,Bailey, K.W.,Sefing, E.J.,Zink, S.,Ziegenbein, J.,Abraham, J.,Helguera, G.,Penichet, M.L.,Gowen, B.B. Host receptor-targeted therapeutic approach to counter pathogenic New World mammarenavirus infections. Nat Commun, 13:558-558, 2022 Cited by PubMed Abstract: Five New World mammarenaviruses (NWMs) cause life-threatening hemorrhagic fever (HF). Cellular entry by these viruses is mediated by human transferrin receptor 1 (hTfR1). Here, we demonstrate that an antibody (ch128.1/IgG1) which binds the apical domain of hTfR1, potently inhibits infection of attenuated and pathogenic NWMs in vitro. Computational docking of the antibody Fab crystal structure onto the known structure of hTfR1 shows an overlapping receptor-binding region shared by the Fab and the viral envelope glycoprotein GP1 subunit that binds hTfR1, and we demonstrate competitive inhibition of NWM GP1 binding by ch128.1/IgG1 as the principal mechanism of action. Importantly, ch128.1/IgG1 protects hTfR1-expressing transgenic mice against lethal NWM challenge. Additionally, the antibody is well-tolerated and only partially reduces ferritin uptake. Our findings provide the basis for the development of a novel, host receptor-targeted antibody therapeutic broadly applicable to the treatment of HF of NWM etiology. PubMed: 35091550DOI: 10.1038/s41467-021-27949-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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