Crystal structure of glycoprotein E2 from bovine viral diarrhea virus.

Publication Type:

Journal Article


Proc Natl Acad Sci U S A, Volume 110, Issue 17, p.6805-10 (2013)


Amino Acid Sequence, Crystallography, X-Ray, Diarrhea Virus 1, Bovine Viral, Epitope Mapping, Models, Molecular, Molecular Sequence Data, Protein Conformation, Viral Envelope Proteins, Virus Internalization


<p>Pestiviruses, including bovine viral diarrhea virus, are important animal pathogens and are closely related to hepatitis C virus, which remains a major global health threat. They have an outer lipid envelope bearing two glycoproteins, E1 and E2, required for cell entry. They deliver their genome into the host cell cytoplasm by fusion of their envelope with a cellular membrane. The crystal structure of bovine viral diarrhea virus E2 reveals a unique protein architecture consisting of two Ig-like domains followed by an elongated β-stranded domain with a new fold. E2 forms end-to-end homodimers with a conserved C-terminal motif rich in aromatic residues at the contact. A disulfide bond across the interface explains the acid resistance of pestiviruses and their requirement for a redox activation step to initiate fusion. From the structure of E2, we propose alternative possible membrane fusion mechanisms. We expect the pestivirus fusion apparatus to be conserved in hepatitis C virus.</p>