Structure of the hepatitis C virus E1E2 glycoprotein complex
Structure of the hepatitis C virus E1E2 glycoprotein complex
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.
Antibodies, Neutralizing, Antiviral Agents/pharmacology, Broadly Neutralizing Antibodies, Cryoelectron Microscopy, Hepacivirus, Hepatitis C, Humans, Liver Neoplasms, Vaccines, Viral Envelope Proteins
263-269
Torrents de la Peña, Alba
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Sliepen, Kwinten
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Eshun-Wilson, Lisa
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Newby, Maddy L.
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Allen, Joel D.
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Zon, Ian
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Koekkoek, Sylvie
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Chumbe, Ana
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Crispin, Max
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Schinkel, Janke
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Lander, Gabriel C.
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Sanders, Rogier W.
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Ward, Andrew B.
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21 October 2022
Torrents de la Peña, Alba
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Sliepen, Kwinten
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Eshun-Wilson, Lisa
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Newby, Maddy L.
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Allen, Joel D.
c89d5569-7659-4835-b535-c9586e956b3a
Zon, Ian
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Koekkoek, Sylvie
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Chumbe, Ana
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Crispin, Max
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Schinkel, Janke
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Lander, Gabriel C.
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Sanders, Rogier W.
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Ward, Andrew B.
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Torrents de la Peña, Alba, Sliepen, Kwinten, Eshun-Wilson, Lisa, Newby, Maddy L., Allen, Joel D., Zon, Ian, Koekkoek, Sylvie, Chumbe, Ana, Crispin, Max, Schinkel, Janke, Lander, Gabriel C., Sanders, Rogier W. and Ward, Andrew B.
(2022)
Structure of the hepatitis C virus E1E2 glycoprotein complex.
Science (New York, N.Y.), 378 (6617), .
(doi:10.1101/2021.12.16.472992).
Abstract
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.
Text
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More information
Accepted/In Press date: 27 September 2022
Published date: 21 October 2022
Keywords:
Antibodies, Neutralizing, Antiviral Agents/pharmacology, Broadly Neutralizing Antibodies, Cryoelectron Microscopy, Hepacivirus, Hepatitis C, Humans, Liver Neoplasms, Vaccines, Viral Envelope Proteins
Identifiers
Local EPrints ID: 474549
URI: http://eprints.soton.ac.uk/id/eprint/474549
ISSN: 0036-8075
PURE UUID: 9557ed02-5601-4bbe-b2ba-fe5ac561f181
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Date deposited: 24 Feb 2023 17:37
Last modified: 02 May 2024 02:00
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Contributors
Author:
Alba Torrents de la Peña
Author:
Kwinten Sliepen
Author:
Lisa Eshun-Wilson
Author:
Maddy L. Newby
Author:
Ian Zon
Author:
Sylvie Koekkoek
Author:
Ana Chumbe
Author:
Janke Schinkel
Author:
Gabriel C. Lander
Author:
Rogier W. Sanders
Author:
Andrew B. Ward
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