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

Oliver W Bayfield; Alasdair C Steven; Alfred A Antson

doi:10.7554/eLife.55517

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

Oliver W Bayfield, Alasdair C Steven, Alfred A Antson

Chemistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e55517
Number of pages	12
Journal	eLife
Volume	9
Early online date	14 Apr 2020
DOIs	https://doi.org/10.7554/eLife.55517
Publication status	E-pub ahead of print - 14 Apr 2020

Bibliographical note

Access to Document

10.7554/eLife.55517

elife-55517-v1
© 2020 eLife Sciences Publications Ltd.
Accepted author manuscript, 16.6 MBLicence: Unspecified
Cryo-EM structure in situ reveals a molecular switch that safeguards virus against genome lossFinal published version, 5.69 MBLicence: CC0

Cite this

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

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.",

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AB - 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.

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