IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36234-4.html
   My bibliography  Save this article

Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes

Author

Listed:
  • Taniya Bhardwaj

    (Indian Institute of Technology Mandi)

  • Kundlik Gadhave

    (Indian Institute of Technology Mandi)

  • Shivani K. Kapuganti

    (Indian Institute of Technology Mandi)

  • Prateek Kumar

    (Indian Institute of Technology Mandi)

  • Zacharias Faidon Brotzakis

    (University of Cambridge)

  • Kumar Udit Saumya

    (Indian Institute of Technology Mandi)

  • Namyashree Nayak

    (Indian Institute of Technology Mandi)

  • Ankur Kumar

    (Indian Institute of Technology Mandi)

  • Richa Joshi

    (Indian Institute of Technology Mandi)

  • Bodhidipra Mukherjee

    (Indian Institute of Technology Mandi)

  • Aparna Bhardwaj

    (Indian Institute of Technology Mandi)

  • Krishan Gopal Thakur

    (CSIR-Institute of Microbial Technology)

  • Neha Garg

    (Banaras Hindu University)

  • Michele Vendruscolo

    (University of Cambridge)

  • Rajanish Giri

    (Indian Institute of Technology Mandi)

Abstract

The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge of the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in the SARS-CoV and SARS-CoV-2 proteomes. An initial analysis using a panel of sequence-based predictors suggested the presence of multiple aggregation-prone regions (APRs) in these proteomes and revealed a strong aggregation propensity in some SARS-CoV-2 proteins. We then studied the in vitro aggregation of predicted aggregation-prone SARS-CoV and SARS-CoV-2 proteins and protein regions, including the signal sequence peptide and fusion peptides 1 and 2 of the spike protein, a peptide from the NSP6 protein, and the ORF10 and NSP11 proteins. Our results show that these peptides and proteins can form amyloid aggregates. We used circular dichroism spectroscopy to reveal the presence of β-sheet rich cores in aggregates and X-ray diffraction and Raman spectroscopy to confirm the formation of amyloid structures. Furthermore, we demonstrated that SARS-CoV-2 NSP11 aggregates are toxic to mammalian cell cultures. These results motivate further studies about the possible role of aggregation of SARS proteins in protein misfolding diseases and other human conditions.

Suggested Citation

  • Taniya Bhardwaj & Kundlik Gadhave & Shivani K. Kapuganti & Prateek Kumar & Zacharias Faidon Brotzakis & Kumar Udit Saumya & Namyashree Nayak & Ankur Kumar & Richa Joshi & Bodhidipra Mukherjee & Aparna, 2023. "Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36234-4
    DOI: 10.1038/s41467-023-36234-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36234-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-36234-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alison Abbott, 2020. "Are infections seeding some cases of Alzheimer’s disease?," Nature, Nature, vol. 587(7832), pages 22-25, November.
    2. Kariem Ezzat & Maria Pernemalm & Sandra Pålsson & Thomas C. Roberts & Peter Järver & Aleksandra Dondalska & Burcu Bestas & Michal J. Sobkowiak & Bettina Levänen & Magnus Sköld & Elizabeth A. Thompson , 2019. "The viral protein corona directs viral pathogenesis and amyloid aggregation," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    3. Mirren Charnley & Saba Islam & Guneet K. Bindra & Jeremy Engwirda & Julian Ratcliffe & Jiangtao Zhou & Raffaele Mezzenga & Mark D. Hulett & Kyunghoon Han & Joshua T. Berryman & Nicholas P. Reynolds, 2022. "Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Fabrizio Chiti & Massimo Stefani & Niccolò Taddei & Giampietro Ramponi & Christopher M. Dobson, 2003. "Rationalization of the effects of mutations on peptide andprotein aggregation rates," Nature, Nature, vol. 424(6950), pages 805-808, August.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Dongtak Lee & Hyo Gi Jung & Dongsung Park & Junho Bang & Da Yeon Cheong & Jae Won Jang & Yonghwan Kim & Seungmin Lee & Sang Won Lee & Gyudo Lee & Yeon Ho Kim & Ji Hye Hong & Kyo Seon Hwang & Jeong Hoo, 2024. "Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Elodie Monsellier & Matteo Ramazzotti & Niccolò Taddei & Fabrizio Chiti, 2008. "Aggregation Propensity of the Human Proteome," PLOS Computational Biology, Public Library of Science, vol. 4(10), pages 1-9, October.
    2. Phillips, J.C., 2016. "Autoantibody recognition mechanisms of p53 epitopes," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 451(C), pages 162-170.
    3. Feng Gu & Marie Boisjoli & Mojgan H. Naghavi, 2023. "HIV-1 promotes ubiquitination of the amyloidogenic C-terminal fragment of APP to support viral replication," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. Phillips, J.C., 2014. "Fractals and self-organized criticality in proteins," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 415(C), pages 440-448.
    5. Espinoza Ortiz, J.S. & Dias, Cristiano L., 2018. "Cooperative fibril model: Native, amyloid-like fibril and unfolded states of proteins," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 511(C), pages 154-165.
    6. Qi Wang & Joshua L Johnson & Nathalie YR Agar & Jeffrey N Agar, 2008. "Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival," PLOS Biology, Public Library of Science, vol. 6(7), pages 1-19, July.
    7. Einav Tayeb-Fligelman & Jeannette T. Bowler & Christen E. Tai & Michael R. Sawaya & Yi Xiao Jiang & Gustavo Garcia & Sarah L. Griner & Xinyi Cheng & Lukasz Salwinski & Liisa Lutter & Paul M. Seidler &, 2023. "Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Hernán Ramos & Lucrecia Moreno & María Gil & Gemma García-Lluch & José Sendra-Lillo & Mónica Alacreu, 2021. "Pharmacists’ Knowledge of Factors Associated with Dementia: The A-to-Z Dementia Knowledge List," IJERPH, MDPI, vol. 18(19), pages 1-18, September.
    9. Allen W Bryan Jr. & Matthew Menke & Lenore J Cowen & Susan L Lindquist & Bonnie Berger, 2009. "BETASCAN: Probable β-amyloids Identified by Pairwise Probabilistic Analysis," PLOS Computational Biology, Public Library of Science, vol. 5(3), pages 1-11, March.
    10. Chyn Liaw & Chun-Wei Tung & Shinn-Ying Ho, 2013. "Prediction and Analysis of Antibody Amyloidogenesis from Sequences," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-15, January.
    11. Carlos Família & Sarah R Dennison & Alexandre Quintas & David A Phoenix, 2015. "Prediction of Peptide and Protein Propensity for Amyloid Formation," PLOS ONE, Public Library of Science, vol. 10(8), pages 1-16, August.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36234-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.