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Taurine Is Covalently Incorporated into Alpha-Tubulin.

ABSTRACT: Taurine is the most abundant free amino acid in the human body. It is found in relatively high concentrations (1-10 mM) in many animal tissues but not in plants. It has been studied since the early 1800s but has not been found to be covalently incorporated into proteins in any animal tissue. Taurine has been found in only one macromolecular complex as a post-transcriptional modification to mitochondrial tRNA. Tubulin is the subunit of microtubules found in all eukaryotic species and almost all eukaryotic cells and subject to numerous post-translational modifications (PTMs). An important PTM on α-tubulin is the removal and re-ligation of the final carboxyl residue, tyrosine. We here demonstrate that taurine can be covalently incorporated at the C-terminal end of alpha-tubulin in avian erythrocytes in a reaction that requires the de-tyrosination PTM and prevents the re-tyrosination PTM. Further, this is, to our knowledge, the first instance of taurine incorporation into a large protein.

SUBMITTER: Olson MT

PROVIDER: S-EPMC8489981 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Taurine is covalently incorporated into alpha tubulin

Project description:Taurine is covalently incorporated into alpha tubulin

2020-04-27 | MSV000085344 | MassIVE

Parthenolide Destabilizes Microtubules by Covalently Modifying Tubulin.

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Project description:Ionogels refer to an emerging composite material made from the confinement of ionic liquids within some specific cross-linked network matrices. They have potential applications in areas such as electrochemical and optical-electric materials. Incorporation of lanthanide (Eu3+, Tb3+) complexes covalently functionalized multi-walled carbon nanotubes (MWCNTs) in ionogels provide new ideas to design and synthesize novel luminescent hybrid materials that have excellent characteristics of luminescence and ionic conductivity. Here, the multifunctional ionogels were synthesized by confining an ionic liquid and the rare earth functionalized MWCNTs in the cross-linked polymethyl methacrylate (PMMA) networks, resulting in a novel optical/electric multifunctional hybrid material. The SEM images and digital photographs suggest that the lanthanide functionalized MWCNTs are evenly dispersed in the hybrid matrices, thus leading to a certain transparency bulky gel. The resulting ionogels exhibit certain viscosity and flexibility, and display an intense red/green emission under UV-light irradiation. The intrinsic conductibility of the embedded ionic liquids and carbon nanotubes in conjunction with the outstanding photoluminescent properties of lanthanide complexes makes the soft hybrid gels a material with great potential and valuable application in the field of optical-electric materials.

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Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin with tubulin degradation effect.

Project description:Microtubules, composed of αβ-tubulin heterodimers, have remained popular anticancer targets for decades. Six known binding sites on tubulin dimers have been identified thus far, with five sites on β-tubulin and only one site on α-tubulin, hinting that compounds binding to α-tubulin are less well characterized. Cevipabulin, a microtubule-active antitumor clinical candidate, is widely accepted as a microtubule-stabilizing agent by binding to the vinblastine site. Our x-ray crystallography study reveals that, in addition to binding to the vinblastine site, cevipabulin also binds to a new site on α-tubulin. We find that cevipabulin at this site pushes the αT5 loop outward, making the nonexchangeable GTP exchangeable, which reduces the stability of tubulin, leading to its destabilization and degradation. Our results confirm the existence of a new agent binding site on α-tubulin and shed light on the development of tubulin degraders as a new generation of antimicrotubule drugs targeting this novel site.

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Dinitroanilines bind alpha-tubulin to disrupt microtubules.

Project description:Protozoan parasites are remarkably sensitive to dinitroanilines such as oryzalin, which disrupt plant but not animal microtubules. To explore the basis of dinitroaniline action, we isolated 49 independent resistant Toxoplasma gondii lines after chemical mutagenesis. All 23 of the lines that we examined harbored single point mutations in alpha-tubulin. These point mutations were sufficient to confer resistance when transfected into wild-type parasites. Several mutations were in the M or N loops, which coordinate protofilament interactions in the microtubule, but most of the mutations were in the core of alpha-tubulin. Docking studies predict that oryzalin binds with an average affinity of 23 nM to a site located beneath the N loop of Toxoplasma alpha-tubulin. This binding site included residues that were mutated in several resistant lines. Moreover, parallel analysis of Bos taurus alpha-tubulin indicated that oryzalin did not interact with this site and had a significantly decreased, nonspecific affinity for vertebrate alpha-tubulin. We propose that the dinitroanilines act through a novel mechanism, by disrupting M-N loop contacts. These compounds also represent the first class of drugs that act on alpha-tubulin function.

| S-EPMC379290 | biostudies-literature

MEC-17 is an alpha-tubulin acetyltransferase.

Project description:In most eukaryotic cells, subsets of microtubules are adapted for specific functions by post-translational modifications (PTMs) of tubulin subunits. Acetylation of the epsilon-amino group of K40 on alpha-tubulin is a conserved PTM on the luminal side of microtubules that was discovered in the flagella of Chlamydomonas reinhardtii. Studies on the significance of microtubule acetylation have been limited by the undefined status of the alpha-tubulin acetyltransferase. Here we show that MEC-17, a protein related to the Gcn5 histone acetyltransferases and required for the function of touch receptor neurons in Caenorhabditis elegans, acts as a K40-specific acetyltransferase for alpha-tubulin. In vitro, MEC-17 exclusively acetylates K40 of alpha-tubulin. Disruption of the Tetrahymena MEC-17 gene phenocopies the K40R alpha-tubulin mutation and makes microtubules more labile. Depletion of MEC-17 in zebrafish produces phenotypes consistent with neuromuscular defects. In C. elegans, MEC-17 and its paralogue W06B11.1 are redundantly required for acetylation of MEC-12 alpha-tubulin, and contribute to the function of touch receptor neurons partly via MEC-12 acetylation and partly via another function, possibly by acetylating another protein. In summary, we identify MEC-17 as an enzyme that acetylates the K40 residue of alpha-tubulin, the only PTM known to occur on the luminal surface of microtubules.

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