Design and evaluation of a tripartite chemogenetic fluorescent reporter for visualizing ternary protein complexes

Abstract Most cellular processes are carried out by multiprotein assemblies. Although various molecular tools exist to visualize binary protein interactions in live cells, the visualization of multiprotein complexes remains a challenge. Here, we report the engineering of a complementation-based appr...

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Bibliographic Details
Main Authors: Sara Bottone, Fanny Broch, Antoine Gedeon, Aurélien Brion, Lina El Hajji, Hela Benaissa, Arnaud Gautier
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62241-8
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Summary:Abstract Most cellular processes are carried out by multiprotein assemblies. Although various molecular tools exist to visualize binary protein interactions in live cells, the visualization of multiprotein complexes remains a challenge. Here, we report the engineering of a complementation-based approach allowing one to visualize the interaction of three proteins through effective proximity-induced complementation of three fragments of pFAST, a chemogenetic fluorescent reporter that binds and stabilizes the fluorescent state of fluorogenic chromophores (so-called fluorogens). This tripartite-split-pFAST allowed the observation of dynamic ternary protein complexes in the cytosol, at the plasma membrane, in the nucleus and at the junction of multiple organelles, opening prospects to study the role and function of multiprotein complexes in live cells and in various biologically relevant contexts.
ISSN:2041-1723