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NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein

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...

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Autores principales: Sutherland, Danica M., Strebl, Michael, Koehler, Melanie, Welsh, Olivia L., Yu, Xinzhe, Hu, Liya, dos Santos Natividade, Rita, Knowlton, Jonathan J., Taylor, Gwen M., Moreno, Rodolfo A., Wörz, Patrick, Lonergan, Zachery R., Aravamudhan, Pavithra, Guzman-Cardozo, Camila, Kour, Sukhleen, Pandey, Udai Bhan, Alsteens, David, Wang, Zhao, Prasad, B. V. Venkataram, Stehle, Thilo, Dermody, Terence S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268256/
https://www.ncbi.nlm.nih.gov/pubmed/37276413
http://dx.doi.org/10.1073/pnas.2219404120
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author Sutherland, Danica M.
Strebl, Michael
Koehler, Melanie
Welsh, Olivia L.
Yu, Xinzhe
Hu, Liya
dos Santos Natividade, Rita
Knowlton, Jonathan J.
Taylor, Gwen M.
Moreno, Rodolfo A.
Wörz, Patrick
Lonergan, Zachery R.
Aravamudhan, Pavithra
Guzman-Cardozo, Camila
Kour, Sukhleen
Pandey, Udai Bhan
Alsteens, David
Wang, Zhao
Prasad, B. V. Venkataram
Stehle, Thilo
Dermody, Terence S.
author_facet Sutherland, Danica M.
Strebl, Michael
Koehler, Melanie
Welsh, Olivia L.
Yu, Xinzhe
Hu, Liya
dos Santos Natividade, Rita
Knowlton, Jonathan J.
Taylor, Gwen M.
Moreno, Rodolfo A.
Wörz, Patrick
Lonergan, Zachery R.
Aravamudhan, Pavithra
Guzman-Cardozo, Camila
Kour, Sukhleen
Pandey, Udai Bhan
Alsteens, David
Wang, Zhao
Prasad, B. V. Venkataram
Stehle, Thilo
Dermody, Terence S.
author_sort Sutherland, Danica M.
collection PubMed
description 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.
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spelling pubmed-102682562023-12-05 NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein Sutherland, Danica M. Strebl, Michael Koehler, Melanie Welsh, Olivia L. Yu, Xinzhe Hu, Liya dos Santos Natividade, Rita Knowlton, Jonathan J. Taylor, Gwen M. Moreno, Rodolfo A. Wörz, Patrick Lonergan, Zachery R. Aravamudhan, Pavithra Guzman-Cardozo, Camila Kour, Sukhleen Pandey, Udai Bhan Alsteens, David Wang, Zhao Prasad, B. V. Venkataram Stehle, Thilo Dermody, Terence S. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2023-06-05 2023-06-13 /pmc/articles/PMC10268256/ /pubmed/37276413 http://dx.doi.org/10.1073/pnas.2219404120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Sutherland, Danica M.
Strebl, Michael
Koehler, Melanie
Welsh, Olivia L.
Yu, Xinzhe
Hu, Liya
dos Santos Natividade, Rita
Knowlton, Jonathan J.
Taylor, Gwen M.
Moreno, Rodolfo A.
Wörz, Patrick
Lonergan, Zachery R.
Aravamudhan, Pavithra
Guzman-Cardozo, Camila
Kour, Sukhleen
Pandey, Udai Bhan
Alsteens, David
Wang, Zhao
Prasad, B. V. Venkataram
Stehle, Thilo
Dermody, Terence S.
NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
title NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
title_full NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
title_fullStr NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
title_full_unstemmed NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
title_short NgR1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
title_sort ngr1 binding to reovirus reveals an unusual bivalent interaction and a new viral attachment protein
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268256/
https://www.ncbi.nlm.nih.gov/pubmed/37276413
http://dx.doi.org/10.1073/pnas.2219404120
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