Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-Like Family Glutamylases
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Published Date:May 07 2015
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Publisher's site:
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Source:Cell. 2015; 161(5):1112-1123.
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Personal Authors:
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Keywords:
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Pubmed ID:25959773
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Pubmed Central ID:PMC4465277
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Description:Glutamylation, the most prevalent tubulin posttranslational modification, marks stable microtubules and regulates recruitment and activity of microtubule- interacting proteins. Nine enzymes of the tubulin tyrosine ligase-like (TTLL) family catalyze glutamylation. TTLL7, the most abundant neuronal glutamylase, adds glutamates preferentially to the β-tubulin tail. Coupled with ensemble and single-molecule biochemistry, our hybrid X-ray and cryo-electron microscopy structure of TTLL7 bound to the microtubule delineates a tripartite microtubule recognition strategy. The enzyme uses its core to engage the disordered anionic tails of α- and β-tubulin, and a flexible cationic domain to bind the microtubule and position itself for β-tail modification. Furthermore, we demonstrate that all single-chain TTLLs with known glutamylase activity utilize a cationic microtubule-binding domain analogous to that of TTLL7. Therefore, our work reveals the combined use of folded and intrinsically disordered substrate recognition elements as the molecular basis for specificity among the enzymes primarily responsible for chemically diversifying cellular microtubules.
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Funding:GM095573/GM/NIGMS NIH HHS/United States
P41 GM103310/GM/NIGMS NIH HHS/United States
DP2 EB020402/EB/NIBIB NIH HHS/United States
DP2 EB020402/DP/NCCDPHP CDC HHS/United States
ZIA NS003122-04/Intramural NIH HHS/United States
R01 GM052468/GM/NIGMS NIH HHS/United States
P41GM103310/GM/NIGMS NIH HHS/United States
R01 GM095573/GM/NIGMS NIH HHS/United States
R37 GM052468/GM/NIGMS NIH HHS/United States
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