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Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate
Mark C Derbyshire1, Sylvain Raffaele2
1Centre for Crop and Disease Management, School of Molecular and Life Sciences, Curtin University, Perth, Australia.
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 in the Pezizomycotina subphylum. 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.
Insights
Fungal effectors evolve robust structures by altering surface residue interactions. This allows pathogen proteins to maintain function across diverse hosts while enabling new adaptations, explaining their evolutionary success.
Area of Science:
- Molecular biology
- Evolutionary biology
- Structural biology
Background:
- Pathogen effector proteins manipulate host cells for disease.
- Effectors face evolutionary pressure to evade host immunity while remaining functional.
- Mechanisms for effector robustness and evolvability are poorly understood.
Purpose of the Study:
- Investigate the structural basis of fungal effector evolution.
- Identify conserved effector families in Pezizomycotina.
- Elucidate how effectors balance structural stability with adaptability.
Main Methods:
- Bioinformatic analysis of fungal orphan effector candidates.
- Structural analysis of conserved effector families.
- Assessment of thermodynamic frustration in surface residues.
Main Results:
- Identified 62 conserved structure-related families of fungal effectors.
- Observed diversification through mutations affecting surface thermodynamic frustration.
- Mutations enhanced protein robustness and altered binding interfaces.
Conclusions:
- Fungal effectors evolve via modifications in surface thermodynamic frustration.
- This mechanism promotes structural robustness and functional adaptability.
- Provides a model for the evolution of conserved effector structures and new effector families.
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