8R3W

Crystal structure of a homospecific CR57 diabody

Summary for 8R3W

• Entry DOI: 10.2210/pdb8r3w/pdb
• Descriptor: Homospecific Diabody CR57 (2 entities in total)
• Functional Keywords: human monoclonal antibody cr57, diabody, monospecific diabody, rabies antibody, immune system
• Biological source: Homo sapiens
• Total number of polymer chains: 2
• Total formula weight: 56115.90

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

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: 39471803
DOI: 10.1016/j.str.2024.10.002

Experimental method

X-RAY DIFFRACTION (2.38 Å)