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Cited by 7Fungal Infections and StudiesPrion Diseases and Protein MisfoldingProtein Structure and Dynamics

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Peptides derived from gp43, the most antigenic protein from Paracoccidioides brasiliensis, form amyloid fibrils in vitro: implications for vaccine development

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Cardim-Pires, Thyago R., Sant’Anna, Ricardo, Foguel, Debora·2021·Scientific Reports
DOI 10.1038/s41598-021-02898-5PMC PMC8648789

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Abstract

Fungal infection is an important health problem in Latin America, and in Brazil in particular. Paracoccidioides (mainly P. brasiliensis and P. lutzii ) is responsible for paracoccidioidomycosis, a disease that affects mainly the lungs. The glycoprotein gp43 is involved in fungi adhesion to epithelial cells, which makes this protein an interesting target of study . A specific stretch of 15 amino acids that spans the region 181–195 (named P10) of gp43 is an important epitope of gp43 that is being envisioned as a vaccine candidate. Here we show that synthetic P10 forms typical amyloid aggregates in solution in very short times, a property that could hamper vaccine development. Seeds obtained by fragmentation of P10 fibrils were able to induce the aggregation of P4, but not P23, two other peptides derived from gp43. In silico analysis revealed several regions within the P10 sequence that can form amyloid with steric zipper architecture. Besides, in-silico proteolysis studies with gp43 revealed that aggregation-prone, P10-like peptides could be generated by several proteases, which suggests that P10 could be formed under physiological conditions. Considering our data in the context of a potential vaccine development, we redesigned the sequence of P10, maintaining the antigenic region (HTLAIR), but drastically reducing its aggregation propensity.

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Metadata

Authors
Cardim-Pires, T. R., Sant’Anna, R., & Foguel, D.
Affiliations
Universidade Federal do Rio de Janeiro (BR)
Corresponding author
Sant’Anna, Ricardo
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-12-06
Volume
11
Issue
1
Pages
23440-23440
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-02898-5
PMC
PMC8648789
OpenAlex
W4225747504
Cited by
7
References
1
Citations by year
2026: 2 · 2025: 2 · 2023: 2 · 2022: 1
FWCI
0.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (Fellow ship)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Topics
  • Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
Paracoccidioides brasiliensis, gp43, amyloid fibrils, peptide aggregation, paracoccidioidomycosis, vaccine candidate, steric zipper, proteolytic processing, fungal adhesion, epitope mapping
MeSH terms
Vaccine Development, Algorithms, Amyloid, Animals, Epitopes, Antigens, Antigens, Fungal, Antigens, Neoplasm, Circular Dichroism, Computer Simulation, Fungal Proteins, Fungal Vaccines, Glycoproteins, Humans, Paracoccidioides, Paracoccidioidomycosis, Peptides, Protein Conformation, Software, Solvents, Protein Folding, Computational Biology, In Vitro Techniques

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