8r3w

Crystal structure of a homospecific CR57 diabody

spinqualitylabelsall models 8r3w, resolution 2.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8r3w is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.38Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 A resolution, and in complex with RABV-G domain III at 2.70 A 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. Structural insight into rabies virus neutralization revealed by an engineered antibody scaffold.,Kedari A, Iheozor-Ejiofor R, Salminen P, Ugurlu H, Makela AR, Levanov L, Vapalahti O, Hytonen VP, Saksela K, Rissanen I Structure. 2024 Oct 25:S0969-2126(24)00437-4. doi: 10.1016/j.str.2024.10.002. PMID:39471803 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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