4ylr

Publication Abstract from PubMed

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 beta-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 alpha- and beta-tubulin, and a flexible cationic domain to bind the microtubule and position itself for beta-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.

Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-like Family Glutamylases.,Garnham CP, Vemu A, Wilson-Kubalek EM, Yu I, Szyk A, Lander GC, Milligan RA, Roll-Mecak A Cell. 2015 May 21;161(5):1112-23. doi: 10.1016/j.cell.2015.04.003. Epub 2015 May , 7. PMID:25959773^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.