Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors

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 ef...

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Main Authors: Mark C. Derbyshire, Sylvain Raffaele
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-40949-9
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author Mark C. Derbyshire
Sylvain Raffaele
author_facet Mark C. Derbyshire
Sylvain Raffaele
author_sort Mark C. Derbyshire
collection DOAJ
description 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.
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spelling doaj.art-906f45af7b6a47169bcd31e0f4f07d7f2023-11-20T09:58:07ZengNature PortfolioNature Communications2041-17232023-08-0114111310.1038/s41467-023-40949-9Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectorsMark C. Derbyshire0Sylvain Raffaele1Centre for Crop and Disease Management, School of Molecular and Life Sciences, Curtin UniversityLaboratoire des Interactions Plantes Micro-organismes Environnement (LIPME), INRAE, CNRS, Université de ToulouseAbstract 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.https://doi.org/10.1038/s41467-023-40949-9
spellingShingle Mark C. Derbyshire
Sylvain Raffaele
Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
Nature Communications
title Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
title_full Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
title_fullStr Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
title_full_unstemmed Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
title_short Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
title_sort surface frustration re patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
url https://doi.org/10.1038/s41467-023-40949-9
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