7T6X

Cryo-EM structure of full-length hepatitis C virus E1E2 glycoprotein in complex with AR4A, AT12009, and IGH505 Fabs

Summary for 7T6X

• Entry DOI: 10.2210/pdb7t6x/pdb
• EMDB information: 25730
• Descriptor: Envelope glycoprotein E2, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (13 entities in total)
• Functional Keywords: hepatitis c virus, e1e2, viral protein-immune system complex, antibody-antigen complex, viral protein/immune system
• Biological source: Hepacivirus C; More
• Total number of polymer chains: 8
• Total formula weight: 253883.93

Authors

Torrents de la Pena, A.,Ward, A.B.,Eshun-Wilson, L.,Lander, G.C. (deposition date: 2021-12-14, release date: 2022-11-02, Last modification date: 2024-11-06)

Primary citation

Torrents de la Pena, A.,Sliepen, K.,Eshun-Wilson, L.,Newby, M.L.,Allen, J.D.,Zon, I.,Koekkoek, S.,Chumbe, A.,Crispin, M.,Schinkel, J.,Lander, G.C.,Sanders, R.W.,Ward, A.B.
Structure of the hepatitis C virus E1E2 glycoprotein complex.
Science, 378:263-269, 2022

PubMed 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.

PubMed: 36264808
DOI: 10.1126/science.abn9884

Experimental method

ELECTRON MICROSCOPY (3.83 Å)