Hepatitis C virus, Core protein, C-terminal / Hepatitis C virus core protein / Hepatitis C virus, Non-structural protein E2/NS1 / Hepatitis C virus non-structural protein E2/NS1 / Hepatitis C virus, Envelope glycoprotein E1 / Hepatitis C virus envelope glycoprotein E1 Similarity search - Domain/homology
Netherlands Organisation for Scientific Research (NWO)
Netherlands
Citation
Journal: Science / Year: 2022 Title: Structure of the hepatitis C virus E1E2 glycoprotein complex. Authors: Alba Torrents de la Peña / Kwinten Sliepen / Lisa Eshun-Wilson / Maddy L Newby / Joel D Allen / Ian Zon / Sylvie Koekkoek / Ana Chumbe / Max Crispin / Janke Schinkel / Gabriel C Lander / ...Authors: Alba Torrents de la Peña / Kwinten Sliepen / Lisa Eshun-Wilson / Maddy L Newby / Joel D Allen / Ian Zon / Sylvie Koekkoek / Ana Chumbe / Max Crispin / Janke Schinkel / Gabriel C Lander / Rogier W Sanders / Andrew B Ward / 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 ...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.
Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Support film - Film thickness: 50.0 nm / Pretreatment - Type: PLASMA CLEANING
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 40 K / Instrument: FEI VITROBOT MARK IV Details: Blotting time: 5 s; Blotting force: 0; Waiting time: 7 s.
Details
Full-length hepatitis C virus E1E2 glycoprotein complexed with AR4A, AT12009, and IGH505 Fabs and embedded in peptidiscs is diluted in TBS to a final concentration of 0.8 mg/ml.
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Electron microscopy
Microscope
FEI TALOS ARCTICA
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Number grids imaged: 2 / Number real images: 5121 / Average exposure time: 9.0 sec. / Average electron dose: 50.0 e/Å2 Details: images were collected at 250 ms per frame. 36 frames were collected.
Electron beam
Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
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