Structure of the hepatitis C virus E1E2 glycoprotein complex.

Autor: Torrents de la Peña A; Department of Integrative Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Sliepen K; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, 1105 AZ Amsterdam, Netherlands., Eshun-Wilson L; Department of Integrative Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Newby ML; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK., Allen JD; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK., Zon I; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, 1105 AZ Amsterdam, Netherlands., Koekkoek S; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, 1105 AZ Amsterdam, Netherlands., Chumbe A; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, 1105 AZ Amsterdam, Netherlands., Crispin M; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK., Schinkel J; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, 1105 AZ Amsterdam, Netherlands., Lander GC; Department of Integrative Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Sanders RW; Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.; Amsterdam Institute for Infection and Immunity, Infectious Diseases, 1105 AZ Amsterdam, Netherlands.; Weill Medical College of Cornell University, New York, NY 10065, USA., Ward AB; Department of Integrative Structural Biology and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Oct 21; Vol. 378 (6617), pp. 263-269. Date of Electronic Publication: 2022 Oct 20.
DOI: 10.1126/science.abn9884
Abstrakt: Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in humans and afflicts more than 58 million people worldwide. The HCV envelope E1 and E2 glycoproteins are essential for viral entry and comprise the primary antigenic target for neutralizing antibody responses. The molecular mechanisms of E1E2 assembly, as well as how the E1E2 heterodimer binds broadly neutralizing antibodies, remain elusive. Here, we present the cryo-electron microscopy structure of the membrane-extracted full-length E1E2 heterodimer in complex with three broadly neutralizing antibodies-AR4A, AT1209, and IGH505-at ~3.5-angstrom resolution. We resolve the interface between the E1 and E2 ectodomains and deliver a blueprint for the rational design of vaccine immunogens and antiviral drugs.
Databáze: MEDLINE
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