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Article Dans Une Revue EMBO Reports Année : 2017

Molecular interactions between tubulin tails and glutamylases reveal determinants of glutamylation patterns

Résumé

Posttranslational modifications of tubulin currently emerge as key regulators of microtubule functions. Polyglutamylation generates a variety of modification patterns that are essential for controlling microtubule functions in different cell types and organelles, and deregulation of these patterns has been linked to ciliopathies, cancer and neurodegeneration. How the different glutamylating enzymes determine precise modification patterns has so far remained elusive. Using computational modelling, molecular dynamics simulations and mutational analyses we now show how the carboxy-terminal tails of tubulin bind into the active sites of glutamylases. Our models suggest that the glutamylation sites on a-and b-tubulins are determined by the positioning of the tails within the catalytic pocket. Moreover, we found that the binding modes of a-and b-tubulin tails are highly similar, implying that most enzymes could potentially modify both, a-and b-tubulin. This supports a model in which the binding of the enzymes to the entire microtubule lattice, but not the specificity of the C-terminal tubulin tails to their active sites, determines the catalytic speci-ficities of glutamylases.
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Dates et versions

hal-02376259 , version 1 (22-11-2019)

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Kathiresan Natarajan, Sudarshan Gadadhar, Judith Souphron, Maria M. Magiera, Carsten Janke. Molecular interactions between tubulin tails and glutamylases reveal determinants of glutamylation patterns. EMBO Reports, 2017, ⟨10.15252/embr.201643751⟩. ⟨hal-02376259⟩
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