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

  1. Oliver W Bayfield  Is a corresponding author
  2. Alasdair C Steven
  3. Alfred A Antson  Is a corresponding author
  1. University of York, United Kingdom
  2. NIAMS-NIH, United States


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 (

The following data sets were generated

Article and author information

Author details

  1. Oliver W Bayfield

    Chemistry, University of York, York, United Kingdom
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
  2. Alasdair C Steven

    Laboratory of Structural Biology, NIAMS-NIH, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Alfred A Antson

    Chemistry, University of York, York, United Kingdom
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4533-3816


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.

Reviewing Editor

  1. Edward H Egelman, University of Virginia, United States

Publication history

  1. Received: January 27, 2020
  2. Accepted: April 13, 2020
  3. Accepted Manuscript published: April 14, 2020 (version 1)
  4. Version of Record published: May 18, 2020 (version 2)


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.


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  1. Oliver W Bayfield
  2. Alasdair C Steven
  3. Alfred A Antson
Cryo-EM structure in situ reveals a molecular switch that safeguards virus against genome loss
eLife 9:e55517.
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