Evolutionary divergence of enzymatic mechanisms for posttranslational polyglycylation.

Article Details

Citation
Copy to clipboard

Rogowski K, Juge F, van Dijk J, Wloga D, Strub JM, Levilliers N, Thomas D, Bre MH, Van Dorsselaer A, Gaertig J, Janke C

Evolutionary divergence of enzymatic mechanisms for posttranslational polyglycylation.

Cell. 2009 Jun 12;137(6):1076-87. doi: 10.1016/j.cell.2009.05.020.

PubMed ID
19524510 [ View in PubMed
]
Abstract

Polyglycylation is a posttranslational modification that generates glycine side chains on proteins. Here we identify a family of evolutionarily conserved glycine ligases that modify tubulin using different enzymatic mechanisms. In mammals, two distinct enzyme types catalyze the initiation and elongation steps of polyglycylation, whereas Drosophila glycylases are bifunctional. We further show that the human elongating glycylase has lost enzymatic activity due to two amino acid changes, suggesting that the functions of protein glycylation could be sufficiently fulfilled by monoglycylation. Depletion of a glycylase in Drosophila using RNA interference results in adult flies with strongly decreased total glycylation levels and male sterility associated with defects in sperm individualization and axonemal maintenance. A more severe RNAi depletion is lethal at early developmental stages, indicating that protein glycylation is essential. Together with the observation that multiple proteins are glycylated, our functional data point towards a general role of glycylation in protein functions.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Tubulin beta-1 chainQ9H4B7Details
Tubulin beta chainP07437Details
Tubulin alpha-1B chainP68363Details
Tubulin alpha-1A chainQ71U36Details
Tubulin alpha-8 chainQ9NY65Details
Tubulin beta-4B chainP68371Details
Tubulin alpha-1C chainQ9BQE3Details
Tubulin alpha-4A chainP68366Details
Tubulin beta-4A chainP04350Details
Tubulin beta-3 chainQ13509Details
Tubulin alpha-3C/D chainQ13748Details
Tubulin alpha-3E chainQ6PEY2Details
Tubulin beta-2A chainQ13885Details
Tubulin beta-2B chainQ9BVA1Details
Tubulin beta-6 chainQ9BUF5Details
Tubulin monoglycylase TTLL3Q9Y4R7Details