Functional recoding of Chlamydomonas reinhardtii thioredoxin type-h into photosynthetic type-f by switching selectivity determinants

Thioredoxins are ubiquitous disulfide reductases folded as an α/β domain of 100-120 amino acid residues. Functional redox site is composed of a pair of cysteines in a canonical WCGPC pentapeptide exposed at the surface of thioredoxins, that reduces disulfide bonds on target proteins. Several genetic...

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Main Authors: Stéphane D. Lemaire, Gianluca Lombardi, Andrea Mancini, Alessandra Carbone, Julien Henri
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Plant Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fpls.2025.1554272/full
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author Stéphane D. Lemaire
Gianluca Lombardi
Andrea Mancini
Alessandra Carbone
Alessandra Carbone
Julien Henri
author_facet Stéphane D. Lemaire
Gianluca Lombardi
Andrea Mancini
Alessandra Carbone
Alessandra Carbone
Julien Henri
author_sort Stéphane D. Lemaire
collection DOAJ
description Thioredoxins are ubiquitous disulfide reductases folded as an α/β domain of 100-120 amino acid residues. Functional redox site is composed of a pair of cysteines in a canonical WCGPC pentapeptide exposed at the surface of thioredoxins, that reduces disulfide bonds on target proteins. Several genetic isoforms of thioredoxins are phylogenetically classified into seven types, including type-h involved in general functions in the cytosol and type-f specifically associated to photosynthetic functions in chloroplasts. Specialization of thioredoxin function is correlated to its selectivity towards a type-dependent repertoire of protein targets. In this study, we combined biochemical and computational approaches to identify amino acid residues of photosynthetic type-f thioredoxin contributing to target the Calvin-Benson-Bassham cycle enzymes fructose-1,6-bisphosphatase and sedoheptulose-1,7-bisphosphatase. By introducing these residues into the scaffold of type-h thioredoxin, we generated a synthetic chimera of thioredoxin-h active towards photosynthetic fructose-1,6-bisphosphatase in vitro. Our combined computational and experimental approach provides a general pipeline for the design of molecular switches, enabling precise functional control.
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spelling doaj-art-1e53ab2d68d94e9fa7c8db6c07befad02025-08-20T03:02:06ZengFrontiers Media S.A.Frontiers in Plant Science1664-462X2025-03-011610.3389/fpls.2025.15542721554272Functional recoding of Chlamydomonas reinhardtii thioredoxin type-h into photosynthetic type-f by switching selectivity determinantsStéphane D. Lemaire0Gianluca Lombardi1Andrea Mancini2Alessandra Carbone3Alessandra Carbone4Julien Henri5Sorbonne Université, CNRS, Laboratoire de Biologie Computationnelle et Quantitative LCQB, Paris, FranceSorbonne Université, CNRS, Laboratoire de Biologie Computationnelle et Quantitative LCQB, Paris, FranceSorbonne Université, CNRS, Laboratoire de Biologie Computationnelle et Quantitative LCQB, Paris, FranceSorbonne Université, CNRS, Laboratoire de Biologie Computationnelle et Quantitative LCQB, Paris, FranceInstitut Universitaire de France, Paris, FranceSorbonne Université, CNRS, Laboratoire de Biologie Computationnelle et Quantitative LCQB, Paris, FranceThioredoxins are ubiquitous disulfide reductases folded as an α/β domain of 100-120 amino acid residues. Functional redox site is composed of a pair of cysteines in a canonical WCGPC pentapeptide exposed at the surface of thioredoxins, that reduces disulfide bonds on target proteins. Several genetic isoforms of thioredoxins are phylogenetically classified into seven types, including type-h involved in general functions in the cytosol and type-f specifically associated to photosynthetic functions in chloroplasts. Specialization of thioredoxin function is correlated to its selectivity towards a type-dependent repertoire of protein targets. In this study, we combined biochemical and computational approaches to identify amino acid residues of photosynthetic type-f thioredoxin contributing to target the Calvin-Benson-Bassham cycle enzymes fructose-1,6-bisphosphatase and sedoheptulose-1,7-bisphosphatase. By introducing these residues into the scaffold of type-h thioredoxin, we generated a synthetic chimera of thioredoxin-h active towards photosynthetic fructose-1,6-bisphosphatase in vitro. Our combined computational and experimental approach provides a general pipeline for the design of molecular switches, enabling precise functional control.https://www.frontiersin.org/articles/10.3389/fpls.2025.1554272/fullphotosynthesisredox post-translational modificationthioredoxinprotein-protein interactionfunctional determinants
spellingShingle Stéphane D. Lemaire
Gianluca Lombardi
Andrea Mancini
Alessandra Carbone
Alessandra Carbone
Julien Henri
Functional recoding of Chlamydomonas reinhardtii thioredoxin type-h into photosynthetic type-f by switching selectivity determinants
Frontiers in Plant Science
photosynthesis
redox post-translational modification
thioredoxin
protein-protein interaction
functional determinants
title Functional recoding of Chlamydomonas reinhardtii thioredoxin type-h into photosynthetic type-f by switching selectivity determinants
title_full Functional recoding of Chlamydomonas reinhardtii thioredoxin type-h into photosynthetic type-f by switching selectivity determinants
title_fullStr Functional recoding of Chlamydomonas reinhardtii thioredoxin type-h into photosynthetic type-f by switching selectivity determinants
title_full_unstemmed Functional recoding of Chlamydomonas reinhardtii thioredoxin type-h into photosynthetic type-f by switching selectivity determinants
title_short Functional recoding of Chlamydomonas reinhardtii thioredoxin type-h into photosynthetic type-f by switching selectivity determinants
title_sort functional recoding of chlamydomonas reinhardtii thioredoxin type h into photosynthetic type f by switching selectivity determinants
topic photosynthesis
redox post-translational modification
thioredoxin
protein-protein interaction
functional determinants
url https://www.frontiersin.org/articles/10.3389/fpls.2025.1554272/full
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