8R40
Crystal structure of diabody CR57 in complex with rabies virus protein G domain III
Summary for 8R40
| Entry DOI | 10.2210/pdb8r40/pdb |
| Descriptor | Homospecific Diabody CR57, Glycoprotein, GLYCEROL (3 entities in total) |
| Functional Keywords | rabies glycoprotein, antibody-antigen complex, cr57 diabody, antibody, engineered antibody, viral protein |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 4 |
| Total formula weight | 83591.12 |
| Authors | Kedari, A.,Rissanen, I. (deposition date: 2023-11-10, release date: 2024-11-06, Last modification date: 2024-12-18) |
| Primary citation | Kedari, A.,Iheozor-Ejiofor, R.,Salminen, P.,Ugurlu, H.,Makela, A.R.,Levanov, L.,Vapalahti, O.,Hytonen, V.P.,Saksela, K.,Rissanen, I. Structural insight into rabies virus neutralization revealed by an engineered antibody scaffold. Structure, 32:2220-, 2024 Cited by PubMed Abstract: Host-cell entry of the highly pathogenic rabies virus (RABV) is mediated by glycoprotein (G) spikes, which also comprise the primary target for the humoral immune response. RABV glycoprotein (RABV-G) displays several antigenic sites that are targeted by neutralizing monoclonal antibodies (mAbs). In this study, we determined the epitope of a potently neutralizing human mAb, CR57, which we engineered into a diabody format to facilitate crystallization. We report the crystal structure of the CR57 diabody alone at 2.38 Å resolution, and in complex with RABV-G domain III at 2.70 Å resolution. The CR57-RABV-G structure reveals critical interactions at the antigen interface, which target the conserved "KLCGVL" peptide and residues proximal to it on RABV-G. Structural analysis combined with a cell-cell fusion assay demonstrates that CR57 effectively inhibits RABV-G-mediated fusion by obstructing the fusogenic transitions of the spike protein. Altogether, this investigation provides a structural perspective on RABV inhibition by a potently neutralizing human antibody. PubMed: 39471803DOI: 10.1016/j.str.2024.10.002 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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