TY - JOUR TI - Cryo-EM structure in situ reveals a molecular switch that safeguards virus against genome loss AU - Bayfield, Oliver W AU - Steven, Alasdair C AU - Antson, Alfred A A2 - Kuriyan, John A2 - Egelman, Edward H A2 - Egelman, Edward H A2 - Jardine, Paul J VL - 9 PY - 2020 DA - 2020/04/14 SP - e55517 C1 - eLife 2020;9:e55517 DO - 10.7554/eLife.55517 UR - https://doi.org/10.7554/eLife.55517 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. KW - portal protein KW - virus assembly KW - DNA packaging KW - cryo-EM KW - bacteriophage KW - symmetry mismatch JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -