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When evolution tinkers to repress


Co-repressors are essential for regulating transcription in all living organisms. An interdisciplinary team has elucidated the structure of a plant co-repressor named TOPLESS. This work shows that this protein is composed of domains identical to those of other co-repressors but with different properties, illustrating how evolution recovers protein domains to create new functions. This study, which also paves the way for reasoned manipulations of this key protein for adapting plants to the environment, was published on July 11, 2017 in the journal PNAS.

Published on 11 July 2017
Co-repressors are essential for regulating the transcription in all living organisms. They provide a physical link between the transcription factors hanging on the promoters and chromatin remodeling proteins that will play on the structure of chromatin to repress the reading of target genes by the transcriptional machinery. TOPLESS is the founding member of a small family of unique plant co-repressors, originally identified in the model plant Arabidopsis, and involved in many major signaling pathways for plant development and stress response. TOPLESS interacts with its partners because of the presence in these proteins of a particular motif called EAR. Its inactivation in Arabidopsis induces the formation of a plant where the stem is replaced by a root, thus generating a plant with legs on legs!

An interdisciplinary team made up of molecular geneticists, biochemists and structural biologists from the Plants Reproduction and Development Laboratory at ENS Lyon (University of Lyon, CNRS, INRA, ENS Lyon, UCBL) and our laboratory as well as of the European Synchrotron Radiation Facility and EMBL in Grenoble, has now solved and functionally characterized the structure of the part of the Arabidopsis TOPLESS protein allowing interaction with its protein partners.

This work led by Teva Vernoux (RDP, Lyon), Renaud Dumas from our laboratory and Max Nanao (ESRF and EMBL, Grenoble) showed a structure similar to that of rice protein and preserved even in the algae. The high resolution of the structure made it possible to position the site of interaction with the EAR motif of its partners very precisely and the team showed that this interaction capacity is also maintained for a TOPLESS protein isolated from an alga, thus demonstrating the seniority of this primordial function. The comparison of the TOPLESS structure with animal co-repressors has also made it possible to demonstrate that these different co-repressors are constructed by assembling identical domains but in different ways.

This study provides a good example of what the Nobel Prize winner François Jacob had called the do it yourself of evolution in the construction of protein function. The study also provides keys for manipulating this essential function for responses to environmental stresses and to enhance the adaptive potential of crop plants. This could allow plants to avoid ending upside down because of stress! 

The TOPLESS (yellow) and animal TBL1 (red) co-repressors both use an identical domain (LisH domain, superimposed part) but in a different way. While the LisH domain of TBL1 is involved in the direct interaction with other repressors, the TOPLESS domain is connected to a second domain (non-overlapping part) responsible for the interaction with the repressors (blue).
© Renaud Dumas

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