5mhr

T3D reovirus sigma1 complexed with 9BG5 Fab fragments

spinqualitylabelsall models 5mhr, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mhr is a 18 chain structure with sequence from Mus musculus and Reovirus sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q86335_9REOV Publication Abstract from PubMed Reovirus attachment protein sigma1 engages glycan receptors and junctional adhesion molecule-A (JAM-A) and is thought to undergo a conformational change during the proteolytic disassembly of virions to infectious subvirion particles (ISVPs) that accompanies cell entry. The sigma1 protein is also the primary target of neutralizing antibodies. Here we present a structural and functional characterization of two neutralizing antibodies that target sigma1 of serotypes 1 (T1) and 3 (T3) reoviruses. Crystal structures reveal that each antibody engages its cognate sigma1 protein within the head domain via epitopes distinct from the JAM-A-binding site. Surface-plasmon resonance and cell-binding assays indicate that both antibodies likely interfere with JAM-A engagement by steric hindrance. To define the interplay between carbohydrate receptor and antibody binding, we conducted hemagglutination inhibition assays using virions and ISVPs. The glycan-binding site of T1 sigma1 is located in the head domain and is partly occluded by the bound Fab in the crystal structure. The T1-specific antibody inhibited hemagglutination by virions and ISVPs, probably via direct interference with glycan engagement. In contrast to T1 sigma1, the carbohydrate-binding site of T3 sigma1 is located in the tail domain, distal to the antibody epitope. The T3-specific antibody inhibited hemagglutination by T3 virions but not ISVPs, indicating that the antibody- and glycan-binding sites in sigma1 are in closer spatial proximity on virions than on ISVPs. Our results provide direct evidence for a structural rearrangement of sigma1 during virion-to-ISVP conversion and contribute new information about mechanisms of antibody-mediated neutralization of reovirus. IMPORTANCE: Virus attachment proteins mediate binding to host cell receptors, serve critical functions in cell and tissue tropism, and are often targeted by the neutralizing antibody response. The structural investigation of antibody-antigen complexes can provide valuable information for understanding the molecular basis of virus neutralization. Studies with enveloped viruses such as HIV and influenza virus have helped to define sites of vulnerability and guide vaccination strategies. By comparison, less is known about antibody binding to nonenveloped viruses. Here, we structurally investigated two neutralizing antibodies that bind the attachment protein sigma1 of reovirus. We have furthermore characterized the neutralization efficiency, the binding affinity for sigma1, and the effect of the antibodies on reovirus receptor engagement. Our analysis defines reovirus interactions with two neutralizing antibodies, allows us to propose a mechanism by which they block virus infection, and provides evidence for a conformational change in the sigma1 protein during viral cell entry. Structural Insights into Reovirus sigma1 Interactions with Two Neutralizing Antibodies.,Dietrich MH, Ogden KM, Katen SP, Reiss K, Sutherland DM, Carnahan RH, Goff M, Cooper T, Dermody TS, Stehle T J Virol. 2016 Dec 7. pii: JVI.01621-16. PMID:27928010 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoclonal Antibodies 3D structures Virus coat proteins 3D structures

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