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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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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. |
format | Online Article Text |
id | pubmed-10268256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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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