Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding
Edited by Michael G. Rossmann, Purdue University, West Lafayette, IN, and approved June 15, 2009
Abstract
Hepatitis E virus (HEV), a small, non-enveloped RNA virus in the family Hepeviridae, is associated with endemic and epidemic acute viral hepatitis in developing countries. Our 3.5-Å structure of a HEV-like particle (VLP) shows that each capsid protein contains 3 linear domains that form distinct structural elements: S, the continuous capsid; P1, 3-fold protrusions; and P2, 2-fold spikes. The S domain adopts a jelly-roll fold commonly observed in small RNA viruses. The P1 and P2 domains both adopt β-barrel folds. Each domain possesses a potential polysaccharide-binding site that may function in cell-receptor binding. Sugar binding to P1 at the capsid protein interface may lead to capsid disassembly and cell entry. Structural modeling indicates that native T = 3 capsid contains flat dimers, with less curvature than those of T = 1 VLP. Our findings significantly advance the understanding of HEV molecular biology and have application to the development of vaccines and antiviral medications.
Data Availability
Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID 3HAG).
Acknowledgments.
We thank B.V.V. Prasad, J. Pan, R.R. Reed, and C. Ke for valuable discussions, and the staff at CHESS and APS for assistance with data collection. This work was supported by the National Institutes of Health (Y.J.T.), the National Natural Scientific Foundation of China (J.Z.), the Major State Basic Research Development Program of China (C.Y.), the Major State Science and Technology Project of China (C.Y.), the Welch Foundation (Y.J.T.), the Hamill Foundation (Y.J.T.), and by the Kresge Science Initiative Endowment Fund at Rice University.
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Cover image: Pictured is a microbial mat growing near White Creek in Yellowstone National Park. These microbial communities produce lipids with unusually large variations in their deuterium content. Zhang et al. show that such variations likely relate to the different metabolic pathways employed by the microbes and suggest that deuterium variations in ancient lipids could be used to identify pathways of energy metabolism active in the past. See the Feature Article by Xinning Zhang et al. on pages 12580–12586. Image by Alex Sessions.
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© 2009.
Data Availability
Data deposition: The atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID 3HAG).
Submission history
Received: May 1, 2009
Published online: August 4, 2009
Published in issue: August 4, 2009
Keywords
Acknowledgments
We thank B.V.V. Prasad, J. Pan, R.R. Reed, and C. Ke for valuable discussions, and the staff at CHESS and APS for assistance with data collection. This work was supported by the National Institutes of Health (Y.J.T.), the National Natural Scientific Foundation of China (J.Z.), the Major State Basic Research Development Program of China (C.Y.), the Major State Science and Technology Project of China (C.Y.), the Welch Foundation (Y.J.T.), the Hamill Foundation (Y.J.T.), and by the Kresge Science Initiative Endowment Fund at Rice University.
Notes
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0904848106/DCSupplemental.
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Competing Interests
The authors declare no conflict of interest.
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