Export citations UNIMARC BibTeX RIS
The role of post-translational acetylation in the association of ATG8 autophagia protein with microtubules from plant cells
SUMMARY. At the moment, a number of factors are known that can influence the processes of the cell cycle. One of these factors are post-translational modifications (PTMs) of proteins that cause changes in their structure and, as a consequence, functionality and ability to interact with other proteins of the cell, including microtubule proteins. The aim of our work was a comparative analysis of the mechanism of the effect of PTMs on the structure and activity of proteins by the example of the effect of acetylation of Lys40 in α-tubulin TUBA4 from A. thaliana on its interaction with ATG8à. All the studied proteins were reconstructed by homology to the experimentally proven crystal structures. Further comparative analysis of protein-protein interactions was carried out using in silico methods. We have shown that acetylation of α-tubulin at Lys40 leads to stabilization of its structure in comparison with its non-acetylated form. It was also demonstrated using molecular dynamics that the replacement of acetylated α-tubulin in a complex with ATG8 by its non-acetylated form leads to a reduction in the interacting residues and, as a consequence, to a complete breakdown of the contact. Acetylation of α-tubulin at the Lys40 residue leads to the stabilization of both the protein itself and the complex under study with ATG8.
Key words: post-translational modifications, tubulin, ATG8, microtubules, in silico, molecular dynamics
E-mail: rayevsky85 gmail.com
1. Abraham, M.J. and Gready, J.E., Optimization of parameters for molecular dynamics simulation using smooth particle-mesh Ewald in GROMACS 4.5, J. Comp. Chem., 2011, vol. 32, no. 9, pp. 2031–2040.https://doi.org/10.1002/jcc.21773
2. Adamakis, I.-D.S., Panteris, E., and Eleftheriou, E.P., Tubulin acetylation mediates bisphenol a effects on the microtubule arrays of Allium cepa and Triticum turgidum, Biomolecules, 2019, vol. 9, no. 5, p. 185. https://doi.org/10.3390/biom9050185
3. Avin-Wittenberg, T., Honig, A., and Galili, G., Variations on a theme: plant autophagy in comparison to yeast and mammals, Protoplasma, 2012, vol. 249, pp. 285–299.
4. Benkert, P., Tosatto, S.C.E., and Schomburg, D., QM-EAN: a comprehensive scoring function for model quality assessment, Proteins, 2008, vol. 71, no. 1, pp. 261–277.
5. Blume, Y.B., A journey through plant cytoskeleton: hot spots in signaling and functioning, Cell Biol. Int., 2019, vol. 43, no. 9, pp. 978–982. https://doi.org/10.1002/cbin.11210
6. Blume, Y.B., Smertenko, A., Ostapets, N.N., et al., Post-translational modifications of plant tubulin, Cell Biol. Int., 1997, vol. 21, no. 12, pp. 917–920.
7. Bussi, G., Donadio, D., and Parrinello, M., Canonical sampling through velocity rescaling, J. Chem. Phys., 2007, vol. 126, no. 1, p. 014101.https://doi.org/10.1063/1.2408420
8. Chu, C.-W., Hou, F., Zhang, J., et al., A novel acetylation of p-tubulin by San modulates microtubule polymerization via down-regulating tubulin incorporation, Mol. Biol. Cell, 2011, vol. 22, no. 4, pp. 448–456. https://doi.org/10.1091/mbc.e10-03-0203
9. Eshun-Wilson, L., Zhang, R., Portran, D., et al., Effects of α-tubulin acetylation on microtubule structure and stability, Proc. Natl. Acad. Sci. U. S. A., 2019, vol. 116, no. 21, pp. 10366–10371. https://doi.org/10.1073/pnas.1900441116
10. Fass, E., Shvets, E., Degani, I., et al., Microtubules support production of starvation-induced autophagosomes but not their targeting and fusion with lysosomes, J. Biol. Chem., 2006, vol. 281, pp. 36303–36316.
11. Fernandez-Recio, J., Totrov, M., and Abagyan, R., Screened charge electrostatic model in protein–protein docking simulations, Pac. Symp. Biocomput., 2002, vol. 7, pp. 552–563.
12. Fourest-Lieuvin, A., Peris, L., Gache, V., et al., Microtubule regulation in mitosis: tubulin phosphorylation by the cyclin-dependent kinase Cdk1, Mol. Biol. Cell, 2006, vol. 17, pp. 1041–1050. https://doi.org/10.1091/mbc.E05-07-0621
13. Freedman, H., Luchko, T., Luduena, R.F., and Tuszynski, J.A., Molecular dynamics modeling of tubulin C-terminal tail interactions with the microtubule surface, Proteins, 2011, vol. 79, no. 10, pp. 2968–2982. https://doi.org/10.1002/prot.23155
14. Gardiner, J., Posttranslational modification of plant microtubules, Plant Signal. Behav., 2019, vol. 14, p. 10. https://doi.org/10.1080/15592324.2019.1654818
15. Geeraert, C., Ratier, A., and Pfisterer, S.G., Starvation-induced hyperacetylation of tubulin is required for the stimulation of autophagy by nutrient deprivation, J. Biol. Chem., 2010, vol. 285, no. 31, vol. 24184–24194. https://doi.org/10.1074/jbc.m109.091553
16. Geeraert, C., Ratier, A., Pfisterer, S.G., et al., Starvation-induced hyperacetylation of tubulin is required for the stimulation of autophagy by nutrient deprivation, J. Biol. Chem., 2010, vol. 285, no. 31, pp. 24184–24194.
17. Grauffel, C., Stote, R.H., and Dejaegere, A force field parameters for the simulation of modified histone tails, J. Comput. Chem., 2010, vol. 31, no. 13, pp. 2434–2451. https://doi.org/10.1002/jcc.21536
18. Grosdidier, S., Totrov, M., and Fernandez-Recio, J., Computer applications for prediction of protein–protein interactions and rational drug design, Adv. Appl. Bioinform. Chem., 2009, vol. 2, pp. 101–123.
19. Guo, Y., Li, M., Pu, X., et al., PRED_PPI: a server for predicting protein–protein interactions based on sequence data with probability assignment, BMC Res. Notes, 2010, vol. 3, p. 145. https://doi.org/10.1186/1756-0500-3-145
20. Howes, S.C., Alushin, G.M., Shida, T., et al., Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure, Mol. Biol. Cell, 2014, vol. 25, pp. 2, pp. 257–266.https://doi.org/10.1091/mbc.e13-07-0387
21. Jahreiss, L., Menzies, F.M., and Rubinsztein, D.C., The itinerary of autophagosomes: from peripheral formation to kiss-and-run fusion with lysosomes, Traffic, 2008, vol. 9, pp. 574–587.
22. Janke, C. and Montagnac, G., Causes and consequences of microtubule acetylation, Curr. Biol., 2017, vol. 27, no. 23, pp. 1287–1292. https://doi.org/10.10l6/j.cub.2017.10.044
23. Janke, C. and Magiera, M.M., The tubulin code and its role in controlling microtubule properties and functions, Nat. Rev. Mol. Cell Biol., 2020, vol. 21, pp. 307–326. https://doi.org/10.1038/s41580-020-0214-3
24. Ketelaar, T., Voss, C., Dimmock, S.A., et al., Arabidopsis homologues of the autophagy protein Atg8 are a novel family of microtubule binding proteins, FEBS Lett., 2004, vol. 567, nos. 2–3, pp. 302–306. https://doi.org/10.1016/j.febslet.2004.04.088
25. Kirisako, T., Ichimura, Y., Okada, H., et al., The reversible modification regulates the membranebinding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway, J. Cell Biol., 2000, vol. 151, no. 2, pp. 263–276. https://doi.org/10.1083/jcb.151.2.263
26. Kouno, T., Mizuguchi, M., Tanida, I., et al., Solution structure of microtubule-associated protein light chain 3 and identification of its functional subdomains, J. Biol. Chem., 2005, vol. 280, no. 26, vol. 24610–24617. https://doi.org/10.1074/jbc.m413565200
27. Kraft, L.J., Manral, P., Dowler, J., and Kenworthy, A.K., Nuclear LC3 associates with slowly diffusing complexes that survey the nucleolus, Traffic, 2016, vol. 17, no. 4, pp. 369–399.https://doi.org/10.1111/tra.12372
28. Lee, J., Cheng, X., Swails, J.M., et al., CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM simulations using the CHARMM36 additive force field, J. Chem. Theory Comp., 2015, vol. 12, no. 1, pp. 405–413. https://doi.org/10.1021/acs.jctc.5b00935
29. Littauer, U.Z., Giveon, D., Thierauf, M., et al., Common and distinct tubulin binding sites for microtubule-associated proteins, Proc. Natl. Acad. Sci. U. S. A., 1986, vol. 83, no. 19, pp. 7162–7166. https://doi.org/10.1073/pnas.83.19.7162
30. Liu, Y. and Bassham, D.C., Autophagy: pathways for self-eating in plant cells, Annu. Rev. Plant Biol., 2012, vol. 63, pp. 215–237.
31. Lytvyn, D.I. and Blume, Ya.B., Microtubular cytoskeleton in autophagy and programmed cell death development in plants, in Programmed Cell Death in Plants and Animals, Rice, J., Ed., New York: Nova Sci. Publ., pp. 1–26.
32. Lytvyn, D.I., Olenieva, V.D., Yemets, A.I., and Blume, Y.B., Histochemical analysis of tissue-specific α-tubulin acetylation as a response to autophagy induction by different stress factors in Arabidopsis thaliana, Cytol. Genet., 2018, vol. 52, no. 4, pp. 245–252. https://doi.org/10.3103/s0095452718040059
33. Mackeh, R., Perdiz, D., Lorin, S., et al., Autophagy and microtubules—new story, old players, J. Cell Sci., 2013, vol. 126, no. 5, pp. 1071–1080. https://doi.org/10.1242/jcs.115626
34. MacTaggart, B. and Kashina, A., Posttranslational modifications of the cytoskeleton, Cytoskeleton, 2021, pp. 1–32. https://doi.org/10.1002/cm.21679
35. Maruta, H., The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules, J. Cell Biol., 1986, vol. 103, no. 2, pp. 571–579. https://doi.org/10.1083/jcb.103.2.571
36. McEwan, D.G. and Dikic, I., The three musketeers of autophagy: phosphorylation, ubiquitylation and acetylation, Trends Cell Biol., 1986, vol. 21, no. 4, pp. 195–201. https://doi.org/10.1016/j.tcb.2010.12.006
37. Merkulova, E.A., Guiboileau, A., Naya, L., et al., Assessment and optimization of autophagy monitoring methods in Arabidopsis roots indicate direct fusion of autophagosomes with vacuoles, Plant Cell Physiol., 2014, vol. 55, no. 4, pp. 715–726. https://doi.org/10.1093/pcp/pcu041
38. Minoura, I., Hachikubo, Y., Yamakita, Y., et al., Overexpression, purification, and functional analysis of recombinant human tubulin dimer, FEBS Lett., 2013, vol. 587, no. 21, pp. 3450–3455. doihttps://doi.org/10.1016/j.febslet.2013.08.032
39. Monastyrska, I., Rieter, E., Klionsky, D.J., and Reggiori, F., Multiple roles of the cytoskeleton in autophagy, Biol. Rev. Camb. Philos. Soc., 2009, vol. 84, no. 3, pp. 431–448.
40. Noda, N.N., Ohsumi, Y., and Inagaki, F., Crystallographic studies on autophagy-related proteins, in Current Trends in X-Ray Crystallography, Chandrasekaran, A., Ed. IntechOpen, 2011. https://doi.org/10.5772/29509
41. Olenieva, V., Lytvyn, D., Yemets, A., et al., Tubulin acetylation accompanies autophagy development induced by different abiotic stimuli in Arabidopsis thaliana, Cell Biol. Int., 2019, vol. 43, pp. 1056–1064. https://doi.org/10.1002/cbin.10843
42. Parrinello, M. and Rahman, A., Polymorphic transitions in single crystals: a new molecular dynamics method, J. Appl. Phys., 1981, vol. 52, no. 12, pp. 7182–7190. https://doi.org/10.1063/1.328693
43. Parrotta, L., Cresti, M., and Cai, G., Accumulation and posttranslational modifications of plant tubulins, Plant Biol., 2014, vol. 16, no. 3, pp. 521–527.
44. Portran, D., Schaedel, L., Xu, Z., et al., Tubulin acetylation protects long-lived microtubules against mechanical ageing, Nat. Cell Biol., 2017, vol. 19, no. 4, pp. 391–398. https://doi.org/10.1038/ncb3481
45. Raevsky, A.V., Sharifi, M., Samofalova, D.A., et al., 3D structure prediction of histone acetyltransferase proteins of the MYST family and their interactome in Arabidopsis thaliana, J. Mol. Model., 2016, vol. 22, no. 11, p. 256. https://doi.org/10.1007/s00894-016-3103-0
46. Ramkumar, A., Jong, B.Y., and Ori-McKenney, K.M., ReMAPping the microtubule landscape: How phosphorylation dictates the activities of microtubule-associated proteins, Dev. Dyn., 2018, vol. 247, pp. 138–155. https://doi.org/10.1002/dvdy.24599
47. Rayevsky, A., Sharifi, M., Samofalova, D., et al., In silico mechanistic model of microtubule assembly inhibition by selective chromone derivatives, J. Mol. Struct., 2021, p. 1241. https://doi.org/10.1016/j.molstruc.2021.130633
48. Rayevsky, A.V., Sharifi, M., Samofalova, D.A., et al., Structural and functional features of lysine acetylation of plant and animal tubulins, Cell Biol Int., 2019, vol. 43, art. 10401048. https://doi.org/10.1002/cbin.10887
49. Samofalova, D.A., Karpov, P.A., Raevsky, A.V., and Blume, Y.B., Protein phosphatases potentially associated with regulation of microtubules, their spatial structure reconstruction and analysis, Cell Biol. Int., 2019, vol. 43, pp. 1081–1090. https://doi.org/10.1002/cbin.10810
50. Smertenko, A., Blume, Y.B., Viklicky, V., et al., Posttranslational modifications and multiple isoforms of tubulin in Nicotiana tabacum cells, Planta, 1997, vol. 201, no. 3, pp. 349–358.
51. Suzuki, H., Tabata, K., Morita, E., et al., Structural basis of the autophagy-related LC3/Atg13 LIR complex: recognition and interaction mechanism, Structure, 2014, vol. 22, no. 1, pp. 47–58. https://doi.org/10.1016/j.str.2013.09.023
52. Takemura, R., Okabe, S., Umeyama, T., et al., Increased microtubule stability and alpha tubulin acetylation in cells transfected with microtubule-associated proteins MAP1B, MAP2 or tau, J. Cell Sci., 1992, vol. 103, no. 4, pp. 953–964. https://doi.org/10.1242/jcs.103.4.953
53. Tran, H.T., Nimick, M., Uhrig, R.G., et al., Arabidopsis thaliana histone deacetylase 14 (HDA14) is an α-tubulin deacetylase that associates with PP2A and enriches in the microtubule fraction with the putative histone acetyltransferase ELP3, Plant J., 2012, vol. 71, pp. 263–272.
54. Verhey, K.J. and Gaertig, J., The tubulin code, Cell Cycle, 2007, vol. 6, no. 17, pp. 2152–2160.
55. Weiergraber, O.H., Mohrluder, J., and Willbold, D., Atg8 family proteins—autophagy and beyond, in Autophagy—A Double-Edged Sword—Cell Survival or Death?, Bailly, Y., Ed., Rijeka: InTech, 2013, pp. 13–45.
56. Wloga, D., Joachimiak, E., and Fabczak, H., Tubulin post-translational modifications and microtubule dynamics, Int. J. Mol. Sci., 2017, vol. 18, p. 2207. https://doi.org/10.3390/ijms18102207
57. Xu, Z., Schaedel, L., Portran, D., et al., Microtubules acquire resistance from mechanical breakage through intralumenal acetylation, Science, 2017, vol. 356, no. 6335, pp. 328–332. https://doi.org/10.1126/science.aai8764
58. Yoshimoto, K., Beginning to understand auto-phagy, an intracellular self-degradation system in plants, Plant Cell Physiol., 2012, vol. 53, pp. 1355–1365.
59. Zoete, V., Cuendet, M.A., Grosdidier, A., and Michielin, O., SwissParam: a fast force field generation tool for small organic molecules, J. Comp. Chem., 2012, vol. 32, pp. 11, pp. 2359–2368. https://doi.org/10.1002/jcc.21816
|Coded & Designed by Volodymyr Duplij||Modified 01.12.23|