Insights into herpesvirus assembly from the structure of the pUL7:pUL51 complex
Abstract
Herpesviruses acquire their membrane envelopes in the cytoplasm of infected cells via a molecular mechanism that remains unclear. Herpes simplex virus (HSV)-1 proteins pUL7 and pUL51 form a complex required for efficient virus envelopment. We show that interaction between homologues of pUL7 and pUL51 is conserved across human herpesviruses, as is their association with trans-Golgi membranes. We characterized the HSV-1 pUL7:pUL51 complex by solution scattering and chemical crosslinking, revealing a 1:2 complex that can form higher-order oligomers in solution, and we solved the crystal structure of the core pUL7:pUL51 heterodimer. While pUL7 adopts a previously-unseen compact fold, the helix-turn-helix conformation of pUL51 resembles the cellular endosomal complex required for transport (ESCRT)-III component CHMP4B and pUL51 forms ESCRT-III–like filaments, suggesting a direct role for pUL51 in promoting membrane scission during virus assembly. Our results provide a structural framework for understanding the role of the conserved pUL7:pUL51 complex in herpesvirus assembly.
Data availability
Crystallographic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (accession code 6T5A), and raw diffraction images have been deposited in the University of Cambridge Apollo repository (https://doi.org/10.17863/CAM.44914). SAXS data, ab initio models and pseudo-atomic models have been deposited into the Small-Angle Scattering Biological Data Bank (SASBDB) under the accession codes SASDG37 (pUL7:pUL51(8-142) heterotrimer), SASDG47 (pUL7:pUL51 heterohexamer) and SASDG57 (pUL7:pUL51 heterotrimer). Mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD015941. Source data and code for performing evolutionary analysis of the pUL7:pUL51 interaction interface across α-herpesviruses is provided in files Source code 1 and Source data 1.
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Crystal structure of herpes simplex virus 1 pUL7:pUL51 complexProtein Data Bank, 6T5A.
Article and author information
Author details
Funding
Wellcome (098406/Z/12/B)
- Stephen C Graham
Royal Society (098406/Z/12/B)
- Stephen C Graham
Nvidia
- Stephen C Graham
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Wesley I Sundquist, University of Utah School of Medicine, United States
Version history
- Received: November 21, 2019
- Accepted: May 7, 2020
- Accepted Manuscript published: May 11, 2020 (version 1)
- Accepted Manuscript updated: May 12, 2020 (version 2)
- Version of Record published: June 11, 2020 (version 3)
Copyright
© 2020, Butt et al.
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.
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