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

Autor:	Sutherland DM; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.; Institute of Infection, Inflammation, and Immunity, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA 15224., Strebl M; Interfaculty Institute of Biochemistry, University of Tübingen, D-72076 Tübingen, Germany., Koehler M; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium., Welsh OL; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.; Institute of Infection, Inflammation, and Immunity, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA 15224., Yu X; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030., Hu L; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030., Dos Santos Natividade R; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium., Knowlton JJ; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.; Cryo-Electron Microscopy and Tomography Core, Baylor College of Medicine, Houston, TX 77030., Taylor GM; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.; Institute of Infection, Inflammation, and Immunity, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA 15224., Moreno RA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030., Wörz P; Interfaculty Institute of Biochemistry, University of Tübingen, D-72076 Tübingen, Germany., Lonergan ZR; Cryo-Electron Microscopy and Tomography Core, Baylor College of Medicine, Houston, TX 77030., Aravamudhan P; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.; Institute of Infection, Inflammation, and Immunity, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA 15224., Guzman-Cardozo C; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.; Institute of Infection, Inflammation, and Immunity, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA 15224., Kour S; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224., Pandey UB; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232.; Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, PA 15261., Alsteens D; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium.; Children's Neuroscience Institute, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA 15224., Wang Z; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030.; Walloon Excellence in Life Sciences and Biotechnology, 1300 Wavre, Belgium.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030., Prasad BVV; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030.; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030., Stehle T; Interfaculty Institute of Biochemistry, University of Tübingen, D-72076 Tübingen, Germany., Dermody TS; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.; Institute of Infection, Inflammation, and Immunity, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, Pittsburgh, PA 15224.; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Jun 13; Vol. 120 (24), pp. e2219404120. Date of Electronic Publication: 2023 Jun 05.
DOI:	10.1073/pnas.2219404120
Abstrakt:	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.
Databáze:	MEDLINE
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