A pentameric protein ring with novel architecture is required for herpesviral packaging

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Abstract

Genome packaging in large double-stranded DNA viruses requires a powerful molecular motor to force the viral genome into nascent capsids, which involves essential accessory factors that are poorly understood. Here, we present structures of two such accessory factors from the oncogenic herpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV; ORF68) and Epstein-Barr virus (EBV; BFLF1). These homologous proteins form highly similar homopentameric rings with a positively charged central channel that binds double-stranded DNA. Mutation of individual positively charged residues within but not outside the channel ablates DNA binding, and in the context of KSHV infection these mutants fail to package the viral genome or produce progeny virions. Thus, we propose a model in which ORF68 facilitates the transfer of newly replicated viral genomes to the packaging motor.

Data availability

Atomic coordinates and structure factors for ORF68 have been deposited in the Protein Data Bank with accession code 6XF9. Diffraction images have been deposited in the SBGrid Data Bank under ID 794 (https://doi:10.15785/SBGRID/794). Cryo-EM maps for ORF68 and BFLF1 have been deposited in the Electron Microscopy Data Bank with accession codes EMD-22167 and EMD-22168. The atomic model of BFLF1 was deposited in the Protein Data Bank with accession code 6XFA. Final coordinate sets, structure factors with calculated phases, and cryo-EM maps are provided as Supplementary Data 1.

Article and author information

Author details

Allison L Didychuk

Plant & Microbial Biology, University of California Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Stephanie N Gates

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Matthew R Gardner

Department of Plant & Microbial Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.
Lisa M Strong

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-4293-8131
Andreas Martin

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
Andreas Martin, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0003-0923-3284
Britt A Glaunsinger

Department of Plant & Microbial Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
glaunsinger@berkeley.edu

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0003-0479-9377

Funding

Damon Runyon Cancer Research Foundation (DRG-2349-18)

Allison L Didychuk

Damon Runyon Cancer Research Foundation (DRG-2342-18)

Stephanie N Gates

Howard Hughes Medical Institute (n/a)

Andreas Martin
Britt A Glaunsinger

National Institutes of Health (R01AI122528)

Britt A Glaunsinger

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.