Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell. 2015 May 21;161(5):1112-23. doi: 10.1016/j.cell.2015.04.003. Epub 2015 May 7.

Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-like Family Glutamylases.

Author information

1
Cell Biology and Biophysics Unit, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
2
Scripps Research Institute, La Jolla, CA 92037, USA.
3
Cell Biology and Biophysics Unit, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA; National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA. Electronic address: antonina@mail.nih.gov.

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.

Comment in

PMID:
25959773
PMCID:
PMC4465277
DOI:
10.1016/j.cell.2015.04.003
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center