8a1e

Rabies virus glycoprotein in complex with Fab fragments of 17C7 and 1112-1 neutralizing antibodies

spinqualitylabelsall models 8a1e, resolution 2.83Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8a1e is a 5 chain structure with sequence from Homo sapiens, Mus musculus and Rabies virus strain Pasteur vaccin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.83Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GLYCO_RABVP Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein and thereby facilitate rabies virus entry into cells (By similarity). Publication Abstract from PubMed Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-G's pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies that can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-A structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1, that recognize distinct epitopes. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. Targeted mutations can similarly stabilize RABV-G in the pre-fusion conformation, a key step toward structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and this will facilitate the development of improved vaccines and prophylactic antibodies. Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies.,Ng WM, Fedosyuk S, English S, Augusto G, Berg A, Thorley L, Haselon AS, Segireddy RR, Bowden TA, Douglas AD Cell Host Microbe. 2022 Sep 14;30(9):1219-1230.e7. doi: , 10.1016/j.chom.2022.07.014. Epub 2022 Aug 18. PMID:35985336 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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