6i9i

Rift valley fever virus Gn in complex with a neutralizing antibody fragment

spinqualitylabelsall models 6i9i, resolution 1.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6i9i is a 6 chain structure with sequence from Oryctolagus cuniculus and Rift Valley fever virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.98Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GP_RVFVZ Structural component of the virion that interacts with glycoprotein C (PubMed:18715915). It shields the hydrophobic fusion loops of the glycoprotein C, preventing premature fusion (PubMed:29367607). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:18715915, PubMed:29367607). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after endocytosis of the virion (PubMed:21767814). Plays a role in the packaging of ribonucleoproteins and polymerase during virus assembly (PubMed:21445316). Structural component of the virion that interacts with glycoprotein N (PubMed:18715915). Acts as a class II fusion protein that is activated upon acidification and subsequent repositioning of the glycoprotein N (PubMed:29367607). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:18715915, PubMed:29367607). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after endocytosis of the virion (PubMed:21767814). Plays a role in the inhibition of virus-induced apoptosis. Plays a role for virus dissemination in vertebrates. Plays a role for virus dissemination in mosquitoes. May act as a structural virion protein in insects. Publication Abstract from PubMed The Gn subcomponent of the Gn-Gc assembly that envelopes the human and animal pathogen, Rift Valley fever virus (RVFV), is a primary target of the neutralizing antibody response. To better understand the molecular basis for immune recognition, we raised a class of neutralizing monoclonal antibodies (nAbs) against RVFV Gn, which exhibited protective efficacy in a mouse infection model. Structural characterization revealed that these nAbs were directed to the membrane-distal domain of RVFV Gn and likely prevented virus entry into a host cell by blocking fusogenic rearrangements of the Gn-Gc lattice. Genome sequence analysis confirmed that this region of the RVFV Gn-Gc assembly was under selective pressure and constituted a site of vulnerability on the virion surface. These data provide a blueprint for the rational design of immunotherapeutics and vaccines capable of preventing RVFV infection and a model for understanding Ab-mediated neutralization of bunyaviruses more generally. A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus.,Allen ER, Krumm SA, Raghwani J, Halldorsson S, Elliott A, Graham VA, Koudriakova E, Harlos K, Wright D, Warimwe GM, Brennan B, Huiskonen JT, Dowall SD, Elliott RM, Pybus OG, Burton DR, Hewson R, Doores KJ, Bowden TA Cell Rep. 2018 Dec 26;25(13):3750-3758.e4. doi: 10.1016/j.celrep.2018.12.001. PMID:30590046 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures

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