National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI118887
米国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2023 タイトル: NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein. 著者: 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 ...著者: 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 / 要旨: 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.