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Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
Open accessPreprint — published as 10.1038/s41467-023-40949-9
Abstract
Pathogens secrete effector proteins to subvert host physiology and cause disease. Effectors are engaged in a molecular arms race with the host resulting in conflicting evolutionary constraints to manipulate host cells without triggering immune responses. The molecular mechanisms allowing effectors to be at the same time robust and evolvable remain largely enigmatic. Here, we show that 62 conserved structure-related families encompass the majority of fungal orphan effector candidates at the subphylum level. These effectors diversified through changes in patterns of thermodynamic frustration at surface residues. The underlying mutations tended to increase the robustness of the overall effector protein structure while switching potential binding interfaces. This mechanism could explain how conserved effector families maintained biological activity over long evolutionary timespans in different host environments and provides a model for the emergence of sequence-unrelated effector families with conserved structures.
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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Derbyshire, M. C., & Raffaele, S.
- Affiliations
- Curtin University (AU)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Raffaele, Sylvain
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2023-01-07
- Volume
- 14
- Issue
- 1
- Pages
- 5244-5244
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10462633
- OpenAlex
- W4386215836
- Cited by
- 57
- References
- 1
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 14 · 2023: 10
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Australian Government
- Grains Research and Development Corporation (grant CUR00023, CUR00023)
- Agence Nationale de la Recherche (ANR-21-CE20-0030, ANR-21-CE20-0010, ANR‐19, ANR‐21‐CE20‐30, ANR-10-LABX- 41, ANR-21-CE20-10, ANR-11-IDEX, ANR-11-IDEX-0002, ANR-11IDEX-0002-02, ANR-10, 10-LABX-41, ANR‐19‐CE20‐15)
- Curtin University of Technology (CUR00023)
- Government of Western Australia
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Pathogens and Fungal Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- fungal effectors, Pezizomycotina, structural frustration, surface residues, host-pathogen interaction, effector families
- MeSH terms
- Biological Evolution, Humans, Mutation, Thermodynamics
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