5MHR

T3D reovirus sigma1 complexed with 9BG5 Fab fragments

Summary for 5MHR

• Entry DOI: 10.2210/pdb5mhr/pdb
• Descriptor: Viral attachment protein sigma 1, 9BG5 Fab light chain,LOC100046793 protein,MAb 110 light chain, 9BG5 Fab heavy chain (3 entities in total)
• Functional Keywords: reovirus sigma1, virus antibody complex, neutralization, viral protein, immune system
• Biological source: Reovirus sp.; More
• Total number of polymer chains: 18
• Total formula weight: 388387.34

Authors

Stehle, T.,Dietrich, M.H. (deposition date: 2016-11-25, release date: 2017-02-15, Last modification date: 2024-11-20)

Primary citation

Dietrich, M.H.,Ogden, K.M.,Katen, S.P.,Reiss, K.,Sutherland, D.M.,Carnahan, R.H.,Goff, M.,Cooper, T.,Dermody, T.S.,Stehle, T.
Structural Insights into Reovirus sigma 1 Interactions with Two Neutralizing Antibodies.
J. Virol., 91:-, 2017

PubMed Abstract: Reovirus attachment protein σ1 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 σ1 protein is also the primary target of neutralizing antibodies. Here, we present a structural and functional characterization of two neutralizing antibodies that target σ1 of serotype 1 (T1) and serotype 3 (T3) reoviruses. The crystal structures revealed that each antibody engages its cognate σ1 protein within the head domain via epitopes distinct from the JAM-A-binding site. Surface plasmon resonance and cell-binding assays indicated that both antibodies likely interfere with JAM-A engagement by steric hindrance. To define the interplay between the carbohydrate receptor and antibody binding, we conducted hemagglutination inhibition assays using virions and ISVPs. The glycan-binding site of T1 σ1 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 σ1, the carbohydrate-binding site of T3 σ1 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 σ1 are in closer spatial proximity on virions than on ISVPs. Our results provide direct evidence for a structural rearrangement of σ1 during virion-to-ISVP conversion and contribute new information about the mechanisms of antibody-mediated neutralization of reovirus.

PubMed: 27928010
DOI: 10.1128/JVI.01621-16

Experimental method

X-RAY DIFFRACTION (3 Å)