Electron cryo-microscopy of Bacteriophage PR772 reveals the elusive vertex complex and the capsid architecture

  1. Hemanth KN Reddy  Is a corresponding author
  2. Janos Hajdu
  3. Marta Carroni
  4. Martin Svenda  Is a corresponding author
  1. Uppsala University, Sweden
  2. Stockholm University, Sweden

Abstract

Bacteriophage PR772, a member of the Tectiviridae family, has a 70-nm diameter icosahedral protein capsid that encapsulates a lipid membrane, dsDNA, and various internal proteins. An icosahedrally averaged CryoEM reconstruction of the wild-type virion and a localized reconstruction of the vertex region reveal the composition and the structure of the vertex complex along with new protein conformations that play a vital role in maintaining the capsid architecture of the virion. The overall resolution of the virion is 2.75 Å, while the resolution of the protein capsid is 2.3 Å. The conventional penta-symmetron formed by the capsomeres is replaced by a large vertex complex in the pseudo T=25 capsid. All the vertices contain the host-recognition protein, P5; two of these vertices show the presence of the receptor-binding protein, P2. The 3D structure of the vertex complex shows interactions with the viral membrane, indicating a possible mechanism for viral infection.

Data availability

CryoEM Density maps and atomic models that support the findings of this study have been deposited in the Electron Microscopy Database and the Protein Databank with the accession codes EMD-4461 (Whole particle reconstruction), EMD-4462 (Vertex Complex), EMD-10237 (Localized reconstruction of the penton region), EMD-10238 (Focused Classification of the penton region) and PDB ID 6Q5U (Atomic model of the asymmetric unit).

The following data sets were generated

Article and author information

Author details

  1. Hemanth KN Reddy

    Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
    For correspondence
    hemanth.kumar@icm.uu.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4698-8005
  2. Janos Hajdu

    Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  3. Marta Carroni

    Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7697-6427
  4. Martin Svenda

    Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
    For correspondence
    Martin.Svenda@icm.uu.se
    Competing interests
    The authors declare that no competing interests exist.

Funding

Vetenskapsrådet (828-2012-108)

  • Janos Hajdu

Vetenskapsrådet (628-2008-1109)

  • Janos Hajdu

Vetenskapsrådet (822-2010-6157)

  • Janos Hajdu

Vetenskapsrådet (822-2012-5260)

  • Janos Hajdu

Knut och Alice Wallenbergs Stiftelse (KAW-2011.081)

  • Janos Hajdu

European Research Council (ERC-291602)

  • Janos Hajdu

Vetenskapsrådet (349-2011-6488)

  • Janos Hajdu

Vetenskapsrådet (2015-06107)

  • Janos Hajdu

European Structural and Investment Funds (CZ.02.1.01/0.0/0.0/15_003/0000447)

  • Janos Hajdu

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

Reviewing Editor

  1. Sjors HW Scheres, MRC Laboratory of Molecular Biology, United Kingdom

Version history

  1. Received: May 15, 2019
  2. Accepted: September 9, 2019
  3. Accepted Manuscript published: September 12, 2019 (version 1)
  4. Version of Record published: September 18, 2019 (version 2)

Copyright

© 2019, Reddy 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.

Metrics

  • 1,684
    views
  • 248
    downloads
  • 6
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Hemanth KN Reddy
  2. Janos Hajdu
  3. Marta Carroni
  4. Martin Svenda
(2019)
Electron cryo-microscopy of Bacteriophage PR772 reveals the elusive vertex complex and the capsid architecture
eLife 8:e48496.
https://doi.org/10.7554/eLife.48496

Share this article

https://doi.org/10.7554/eLife.48496

Further reading

    1. Epidemiology and Global Health
    Xiaoxin Yu, Roger S Zoh ... David B Allison
    Review Article

    We discuss 12 misperceptions, misstatements, or mistakes concerning the use of covariates in observational or nonrandomized research. Additionally, we offer advice to help investigators, editors, reviewers, and readers make more informed decisions about conducting and interpreting research where the influence of covariates may be at issue. We primarily address misperceptions in the context of statistical management of the covariates through various forms of modeling, although we also emphasize design and model or variable selection. Other approaches to addressing the effects of covariates, including matching, have logical extensions from what we discuss here but are not dwelled upon heavily. The misperceptions, misstatements, or mistakes we discuss include accurate representation of covariates, effects of measurement error, overreliance on covariate categorization, underestimation of power loss when controlling for covariates, misinterpretation of significance in statistical models, and misconceptions about confounding variables, selecting on a collider, and p value interpretations in covariate-inclusive analyses. This condensed overview serves to correct common errors and improve research quality in general and in nutrition research specifically.

    1. Ecology
    2. Epidemiology and Global Health
    Emilia Johnson, Reuben Sunil Kumar Sharma ... Kimberly Fornace
    Research Article

    Zoonotic disease dynamics in wildlife hosts are rarely quantified at macroecological scales due to the lack of systematic surveys. Non-human primates (NHPs) host Plasmodium knowlesi, a zoonotic malaria of public health concern and the main barrier to malaria elimination in Southeast Asia. Understanding of regional P. knowlesi infection dynamics in wildlife is limited. Here, we systematically assemble reports of NHP P. knowlesi and investigate geographic determinants of prevalence in reservoir species. Meta-analysis of 6322 NHPs from 148 sites reveals that prevalence is heterogeneous across Southeast Asia, with low overall prevalence and high estimates for Malaysian Borneo. We find that regions exhibiting higher prevalence in NHPs overlap with human infection hotspots. In wildlife and humans, parasite transmission is linked to land conversion and fragmentation. By assembling remote sensing data and fitting statistical models to prevalence at multiple spatial scales, we identify novel relationships between P. knowlesi in NHPs and forest fragmentation. This suggests that higher prevalence may be contingent on habitat complexity, which would begin to explain observed geographic variation in parasite burden. These findings address critical gaps in understanding regional P. knowlesi epidemiology and indicate that prevalence in simian reservoirs may be a key spatial driver of human spillover risk.