National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI118887
United States
Citation
Journal: Proc Natl Acad Sci U S A / Year: 2023 Title: NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein. Authors: Danica M Sutherland / Michael Strebl / Melanie Koehler / Olivia L Welsh / Xinzhe Yu / Liya Hu / Rita Dos Santos Natividade / Jonathan J Knowlton / Gwen M Taylor / Rodolfo A Moreno / Patrick ...Authors: Danica M Sutherland / Michael Strebl / Melanie Koehler / Olivia L Welsh / Xinzhe Yu / Liya Hu / Rita Dos Santos Natividade / Jonathan J Knowlton / Gwen M Taylor / Rodolfo A Moreno / Patrick Wörz / Zachery R Lonergan / Pavithra Aravamudhan / Camila Guzman-Cardozo / Sukhleen Kour / Udai Bhan Pandey / David Alsteens / Zhao Wang / B V Venkataram Prasad / Thilo Stehle / Terence S Dermody / Abstract: Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent ...Nogo-66 receptor 1 (NgR1) binds a variety of structurally dissimilar ligands in the adult central nervous system to inhibit axon extension. Disruption of ligand binding to NgR1 and subsequent signaling can improve neuron outgrowth, making NgR1 an important therapeutic target for diverse neurological conditions such as spinal crush injuries and Alzheimer's disease. Human NgR1 serves as a receptor for mammalian orthoreovirus (reovirus), but the mechanism of virus-receptor engagement is unknown. To elucidate how NgR1 mediates cell binding and entry of reovirus, we defined the affinity of interaction between virus and receptor, determined the structure of the virus-receptor complex, and identified residues in the receptor required for virus binding and infection. These studies revealed that central NgR1 surfaces form a bridge between two copies of viral capsid protein σ3, establishing that σ3 serves as a receptor ligand for reovirus. This unusual binding interface produces high-avidity interactions between virus and receptor to prime early entry steps. These studies refine models of reovirus cell-attachment and highlight the evolution of viruses to engage multiple receptors using distinct capsid components.
Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 291 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 3.5 seconds before plunging.
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Electron microscopy
Microscope
JEOL 3200FSC
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 27.5 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron optics
Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 4.1 mm
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Image processing
Particle selection
Number selected: 7182
Startup model
Type of model: OTHER
Final reconstruction
Applied symmetry - Point group: I (icosahedral) / Resolution.type: BY AUTHOR / Resolution: 8.9 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: EMAN2 (ver. 2.31) / Number images used: 1648
Initial angle assignment
Type: NOT APPLICABLE
Final angle assignment
Type: NOT APPLICABLE
FSC plot (resolution estimation)
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