Unknown

Dataset Information

0

Mechanism of microtubule lumen entry for the ?-tubulin acetyltransferase enzyme ?TAT1.


ABSTRACT: Microtubules are structural polymers inside of cells that are subject to posttranslational modifications. These posttranslational modifications create functionally distinct subsets of microtubule networks in the cell, and acetylation is the only modification that takes place in the hollow lumen of the microtubule. Although it is known that the ?-tubulin acetyltransferase (?TAT1) is the primary enzyme responsible for microtubule acetylation, the mechanism for how ?TAT1 enters the microtubule lumen to access its acetylation sites is not well understood. By performing biochemical assays, fluorescence and electron microscopy experiments, and computational simulations, we found that ?TAT1 enters the microtubule lumen through the microtubule ends, and through bends or breaks in the lattice. Thus, microtubule structure is an important determinant in the acetylation process. In addition, once ?TAT1 enters the microtubule lumen, the mobility of ?TAT1 within the lumen is controlled by the affinity of ?TAT1 for its acetylation sites, due to the rapid rebinding of ?TAT1 onto highly concentrated ?-tubulin acetylation sites. These results have important implications for how acetylation could gradually accumulate on stable subsets of microtubules inside of the cell.

SUBMITTER: Coombes C 

PROVIDER: S-EPMC5135325 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Mechanism of microtubule lumen entry for the α-tubulin acetyltransferase enzyme αTAT1.

Coombes Courtney C   Yamamoto Ami A   McClellan Mark M   Reid Taylor A TA   Plooster Melissa M   Luxton G W Gant GW   Alper Joshua J   Howard Jonathon J   Gardner Melissa K MK  

Proceedings of the National Academy of Sciences of the United States of America 20161101 46


Microtubules are structural polymers inside of cells that are subject to posttranslational modifications. These posttranslational modifications create functionally distinct subsets of microtubule networks in the cell, and acetylation is the only modification that takes place in the hollow lumen of the microtubule. Although it is known that the α-tubulin acetyltransferase (αTAT1) is the primary enzyme responsible for microtubule acetylation, the mechanism for how αTAT1 enters the microtubule lume  ...[more]

Similar Datasets

| S-EPMC3890346 | biostudies-literature
| S-EPMC2938957 | biostudies-literature
| S-EPMC4726456 | biostudies-literature
| S-EPMC3382010 | biostudies-literature
| S-EPMC4259157 | biostudies-literature
| S-EPMC6201834 | biostudies-literature
| S-EPMC6535015 | biostudies-literature
| S-EPMC11006419 | biostudies-literature
| S-EPMC3511736 | biostudies-literature
| S-EPMC60769 | biostudies-literature