Cryo-EM structure in situ reveals a molecular switch that safeguards virus against genome loss

Abstract
Data availability
Article and author information
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Abstract

The portal protein is a key component of many double-stranded DNA viruses, governing capsid assembly and genome packaging. Twelve subunits of the portal protein define a tunnel, through which DNA is translocated into the capsid. It is unknown how the portal protein functions as a gatekeeper, preventing DNA slippage, whilst allowing its passage into the capsid, and how these processes are controlled. A cryo-EM structure of the portal protein of thermostable virus P23-45, determined in situ in its procapsid-bound state, indicates a mechanism that naturally safeguards the virus against genome loss. This occurs via an inversion of the conformation of the loops that define the constriction in the central tunnel, accompanied by a hydrophilic–hydrophobic switch. The structure also shows how translocation of DNA into the capsid could be modulated by a changing mode of protein–protein interactions between portal and capsid, across a symmetry-mismatched interface.

Data availability

Cryo-EM reconstruction (EMD-4567) and atomic coordinates (PDB 6QJT) have been deposited with the wwPDB (www.wwpdb.org).

The following data sets were generated

1. Bayfield OW
2. Antson AA
(2020) Cryo-EM reconstruction
EM Data Resource, EMD-4567.

https://www.emdataresource.org/EMD-4567
1. Bayfield OW
2. Antson AA
(2020) Atomic coordinates
PDB, 6QJT.

http://www.rcsb.org/structure/6QJT

Article and author information

Author details

Oliver W Bayfield

Chemistry, University of York, York, United Kingdom

For correspondence
oliver.bayfield@york.ac.uk

Competing interests
The authors declare that no competing interests exist.
Alasdair C Steven

Laboratory of Structural Biology, NIAMS-NIH, Bethesda, United States

Competing interests
The authors declare that no competing interests exist.
Alfred A Antson

Chemistry, University of York, York, United Kingdom

For correspondence
fred.antson@york.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4533-3816

Funding

Wellcome (103460)

Oliver W Bayfield

Wellcome (206377)

Alfred A Antson

National Institute of Arthritis and Musculoskeletal and Skin Diseases (Intramural Research Program)

Alasdair C Steven

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

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.