Tubulin engineering by semi-synthesis reveals that polyglutamylation directs detyrosination

Article Article scientifique Article Tubulin engineering by semi-synthesis reveals that polyglutamylation directs detyrosination eng 2023-06-29 2023-06-29 author Ebberink Eduard author Fernandes Ribeiro Da Sil Simao 0009-0003-3846-1304 819791 Département de biochimie (CHIBI) author Hatzopoulos Georgios 0000-0003-4382-4459 author Agashe Ninad author Chang Po-Han author Guidotti Nora author Reichart Timothy M. 0000-0002-4015-1925 author Reymond Luc 0000-0001-5282-9273 author Velluz Marie-Claire 29019 Département de biochimie (CHIBI) author Schneider Fabian 0000-0002-3146-4815 784108 author Pourroy Cédric 0009-0009-1101-126X author Janke Carsten author Gonczy Pierre 742409 author Fierz Beat 0000-0002-2991-3044 author Aumeier Charlotte 0000-0002-0629-1721 893545 Département de biochimie (CHIBI) 1-30 10.1038/s41557-023-01228-8 37386282 1755-4330 https://www.nature.com/articles/s41557-023-01228-8 <p>Microtubules, a critical component of the cytoskeleton, carry post-translational modifications (PTMs) that are important for the regulation of key cellular processes. Long-lived microtubules, in neurons particularly, exhibit both detyrosination of α-tubulin and polyglutamylation. Dysregulation of these PTMs can result in developmental defects and neurodegeneration. Owing to a lack of tools to study the regulation and function of these PTMs, the mechanisms that govern such PTM patterns are not well understood. Here we produce fully functional tubulin carrying precisely defined PTMs within its C-terminal tail. We ligate synthetic α-tubulin tails—which are site-specifically glutamylated—to recombinant human tubulin heterodimers by applying a sortase- and intein-mediated tandem transamidation strategy. Using microtubules reconstituted with these designer tubulins, we find that α-tubulin polyglutamylation promotes its detyrosination by enhancing the activity of the tubulin tyrosine carboxypeptidase vasohibin/small vasohibin-binding protein in a manner dependent on the length of polyglutamyl chains. We also find that modulating polyglutamylation levels in cells results in corresponding changes in detyrosination, corroborating the link between the detyrosination cycle to polyglutamylation.</p> Dewey 540 39 Département de biochimie 144 false 1381 Groupe Aumeier Nature chemistry 8aa9cf65-fa7e-4cdb-bbe2-3b1362c1c094 Article (Published version) Restricted Article-scientifique-from-crossref.pdf 20197037 application/pdf 794c9e6d72ea31248da06b2ed0abf0b7deb83a96f960d3023ef25e1005b0f6b4 restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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Tubulin engineering by semi-synthesis reveals that polyglutamylation directs detyrosination	Nature chemistry			2023	307	1

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Schneider, Fabian