4YLR

Tubulin Glutamylase

Summary for 4YLR

• Entry DOI: 10.2210/pdb4ylr/pdb
• Related: 4YLS
• Descriptor: Tubulin polyglutamylase TTLL7, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: enzyme, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 57693.92

Authors

Garnham, C.P.,Vemu, A.,Wilson-Kubalek, E.M.,Yu, I.,Szyk, A.,Lander, G.C.,Milligan, R.A.,Roll-Mecak, A. (deposition date: 2015-03-05, release date: 2015-06-17, Last modification date: 2024-02-28)

Primary citation

Garnham, C.P.,Vemu, A.,Wilson-Kubalek, E.M.,Yu, I.,Szyk, A.,Lander, G.C.,Milligan, R.A.,Roll-Mecak, A.
Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-like Family Glutamylases.
Cell, 161:1112-1123, 2015

PubMed Abstract: 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.

PubMed: 25959773
DOI: 10.1016/j.cell.2015.04.003

Experimental method

X-RAY DIFFRACTION (2.55 Å)