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

  • 1,563
    Page views
  • 227
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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

Further reading

    1. Epidemiology and Global Health
    Charumathi Sabanayagam, Feng He ... Ching Yu Cheng
    Research Article Updated

    Background:

    Machine learning (ML) techniques improve disease prediction by identifying the most relevant features in multidimensional data. We compared the accuracy of ML algorithms for predicting incident diabetic kidney disease (DKD).

    Methods:

    We utilized longitudinal data from 1365 Chinese, Malay, and Indian participants aged 40–80 y with diabetes but free of DKD who participated in the baseline and 6-year follow-up visit of the Singapore Epidemiology of Eye Diseases Study (2004–2017). Incident DKD (11.9%) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with at least 25% decrease in eGFR at follow-up from baseline. A total of 339 features, including participant characteristics, retinal imaging, and genetic and blood metabolites, were used as predictors. Performances of several ML models were compared to each other and to logistic regression (LR) model based on established features of DKD (age, sex, ethnicity, duration of diabetes, systolic blood pressure, HbA1c, and body mass index) using area under the receiver operating characteristic curve (AUC).

    Results:

    ML model Elastic Net (EN) had the best AUC (95% CI) of 0.851 (0.847–0.856), which was 7.0% relatively higher than by LR 0.795 (0.790–0.801). Sensitivity and specificity of EN were 88.2 and 65.9% vs. 73.0 and 72.8% by LR. The top 15 predictors included age, ethnicity, antidiabetic medication, hypertension, diabetic retinopathy, systolic blood pressure, HbA1c, eGFR, and metabolites related to lipids, lipoproteins, fatty acids, and ketone bodies.

    Conclusions:

    Our results showed that ML, together with feature selection, improves prediction accuracy of DKD risk in an asymptomatic stable population and identifies novel risk factors, including metabolites.

    Funding:

    This study was supported by the National Medical Research Council, NMRC/OFLCG/001/2017 and NMRC/HCSAINV/MOH-001019-00. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    1. Epidemiology and Global Health
    C Kim, Benjamin Chen ... RECOVER Mechanistic Pathways Task Force
    Review Article

    The NIH-funded RECOVER study is collecting clinical data on patients who experience a SARS-CoV-2 infection. As patient representatives of the RECOVER Initiative’s Mechanistic Pathways task force, we offer our perspectives on patient motivations for partnering with researchers to obtain results from mechanistic studies. We emphasize the challenges of balancing urgency with scientific rigor. We recognize the importance of such partnerships in addressing post-acute sequelae of SARS-CoV-2 infection (PASC), which includes ‘long COVID,’ through contrasting objective and subjective narratives. Long COVID’s prevalence served as a call to action for patients like us to become actively involved in efforts to understand our condition. Patient-centered and patient-partnered research informs the balance between urgency and robust mechanistic research. Results from collaborating on protocol design, diverse patient inclusion, and awareness of community concerns establish a new precedent in biomedical research study design. With a public health matter as pressing as the long-term complications that can emerge after SARS-CoV-2 infection, considerate and equitable stakeholder involvement is essential to guiding seminal research. Discussions in the RECOVER Mechanistic Pathways task force gave rise to this commentary as well as other review articles on the current scientific understanding of PASC mechanisms.