1 School of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300401, China; 2 School of Science, Hebei University of Technology, Tianjin 300401, China; 3 College of Electrical and Information Engineering, Quzhou University, Quzhou 324000, China; 4 Key Laboratory of Molecular Biophysics of Hebei Province, Hebei University of Technology, Tianjin 300401, China
Abstract Microtubules are one kind of cytoskeleton that is ubiquitous in eukaryotic cells and is essential for various biological processes, such as intracellular transport, maintenance of cell morphology and cell division. Microtubules are dynamic structures and the basic unit of microtubules is the heterodimer composed of -tubulin and -tubulin. The biological function of microtubules is based on their dynamic polymerization and depolymerization. However, the nucleotide-dependent depolymerization mechanism of microtubules is still unclear. The dynamic instability of microtubules is determined by the interactions between tubulins. In this work, the interactions between tubulins in the microtubule lattice (GDP at the interdimer interface) and in the special GTP-cap structure (GTP at the interdimer interface) are systematically investigated using all-atom molecular dynamics simulation method. The analysis of the tubulin-tubulin and nucleotide-tubulin interactions and binding free energy at different interfaces of microtubule shows that the hydrolysis of GTP can affect the longitudinal interaction between -tubulin and -tubulin at the interdimer interface and the lateral interaction between -tubulins. In particular, the displacement of M loop of -tubulin induced by GTP hydrolysis weakens the lateral interaction between -tubulins. Based on these results, a nucleotide-dependent depolymerization mechanism of microtubule induced by GTP hydrolysis is proposed.
Bingbing Zhang(张冰冰), Ziling Huo(霍子玲), Jiaxi Li(李佳希), Jingyu Qin(覃静宇), and Yizhao Geng(耿轶钊) Depolymerization mechanism of microtubule revealed by nucleotide-dependent changes of longitudinal and lateral interactions 2025 Chin. Phys. B 34 068702
[1] Goode B L, Drubin D G and Barnes G 2000 Curr. Opin. Cell Biol. 12 63 [2] Nogales E 2000 Annu. Rev. Biochem. 69 277 [3] Montecinos-Franjola F, Schuck P and Sackett D L 2016 J. Biol. Chem. 291 9281 [4] Nogales E 2023 Mol. Biol. Cell 34 rt2 [5] Burns R G 1991 Cell Motil. Cytoskeleton 20 181 [6] Löwe J, Li H, Downing K H and Nogales E 2001 J. Mol. Biol. 313 1045 [7] Nogales E, Wolf S G and Downing K H 1998 Nature 391 199 [8] Cleary J M and Hancock W O 2021 Curr. Biol. 31 R560 [9] Mitchison T and Kirschner M 1984 Nature 312 237 [10] Aher A and Akhmanova A 2018 Curr. Opin. Cell Biol. 50 86 [11] Knossow M, Campanacci V, Khodja L A and Gigant B 2020 iScience 23 101511 [12] Howard J and Hyman A A 2003 Nature 422 753 [13] Wang H W and Nogales E 2005 Nature 435 911 [14] Nogales E and Wang H W 2006 Curr. Opin. Struct. Biol. 16 221 [15] Müller-Reichert T, Chrétien D, Severin F and Hyman A A 1998 Proc. Natl. Acad. Sci. USA 95 3661 [16] Melki R, Carlier M F, Pantaloni D and Timasheff S N 1989 Biochemistry 28 9143 [17] Krebs A, Goldie K N and Hoenger A 2005 EMBO Rep. 6 227 [18] Gigant B, Curmi P A, Martin-Barbey C, Charbaut E, Lachkar S, Lebeau L, Siavoshian S, Sobel A and Knossow M 2000 Cell 102 809 [19] Mitchison T J 1988 Annu. Rev. Cell Biol. 4 527 [20] Bennett M J, Chik J K, Slysz GW, Luchko T, Tuszynski J, Sackett D L and Schriemer D C 2009 Biochemistry 48 4858 [21] Driver J W, Geyer E A, Bailey M E, Rice L M and Asbury C L 2017 eLife 6 e28433 [22] Drechsel D N and Kirschner M W 1994 Curr. Biol. 4 1053 [23] Caplow M and Shanks J 1996 Mol. Biol. Cell 7 663 [24] Desai A and Mitchison T J 1997 Annu. Rev. Cell Dev. Biol. 13 83 [25] Dimitrov A, Quesnoit M, Moutel S, Cantaloube I, Poüs C and Perez F 2008 Science 322 1353 [26] Carlier M F, Didry D and Pantaloni D 1987 Biochemistry 26 4428 [27] O’Brien E T, Voter W A and Erickson H P 1987 Biochemistry 26 4148 [28] Panda D, Miller H P and Wilson L 2002 Biochemistry 41 1609 [29] Roostalu J, Thomas C, Cade N I, Kunzelmann S, Taylor I A and Surrey T 2020 eLife 9 e51992 [30] Estévez-Gallego J, Josa-Prado F, Ku S, Buey R M, Balaguer F A, Prota A E, Lucena-Agell D, Kamma-Lorger C, Yagi T, Iwamoto H, Duchesne L, Barasoain I, Steinmetz M O, Chrétien D, Kamimura S, Díaz J F and Oliva M A 2020 eLife 9 e50155 [31] Gudimchuk N B and McIntosh J R 2021 Nat. Rev. Mol. Cell Biol. 22 777 [32] LaFrance B J, Roostalu J, Henkin G, Greber B J, Zhang R, Normanno D, McCollum C O, Surrey T and Nogales E 2022 Proc. Natl. Acad. Sci. USA 119 e2114994119 [33] Gebremichael Y, Chu J W and Voth G A 2008 Biophys. J. 95 2487 [34] Buey R M, Díaz J F and Andreu J M 2006 Biochemistry 45 5933 [35] Rice L M, Montabana E A and Agard D A 2008 Proc. Natl. Acad. Sci. USA 105 5378 [36] Grafmüller A and Voth G A 2011 Structure 19 409 [37] Nogales E, Whittaker M, Milligan R A and Downing K H 1999 Cell 96 79 [38] Li H, DeRosier D J, NicholsonWV, Nogales E and Downing K H 2002 Structure 10 1317 [39] Sui H and Downing K H 2010 Structure 18 1022 [40] Mitra A and Sept D 2008 Biophys. J. 95 3252 [41] Alushin G M, Lander G C, Kellogg E H, Zhang R, Baker D and Nogales E 2014 Cell 157 1117 [42] Manka S W and Moores C A 2018 Nat. Struct. Mol. Biol. 25 607 [43] Tong D and Voth G A 2020 Biophys. J. 118 2938 [44] Zhou J, Wang A, Song Y, Liu N, Wang J, Li Y, Liang X, Li G, Chu H and Wang H W 2023 Nat. Commun. 14 5980 [45] André J R, Clément M J, Adjadj E, Toma F, Curmi P A and Manivet P 2012 J. Comput. Aided Mol. Des. 26 397 [46] Cannariato M, Zizzi E A, Pallante L, Miceli M and Deriu M A 2024 Biomech. Model. Mechanobiol. 23 569 [47] Liu F, Ji Q, Wang H and Wang J 2018 J. Phys. Chem. B 122 11002 [48] Bigman L S and Levy Y 2020 Proc. Natl. Acad. Sci. USA 117 8876 [49] Geng Y Z, Lu L A, Jia N, Zhang B B and Ji Q 2023 Chin. Phys. B 32 108701 [50] Roll-Mecak A 2015 Semin. Cell Dev. Biol. 37 11 [51] Priel A, Tuszynski J A and Woolf N J 2005 Eur. Biophys. J. 35 40 [52] Tuszyński J A, Brown J A, Crawford E, Carpenter E J, Nip M L A, Dixon J M and Satarić M V 2005 Math. Comput. Model. 41 1055 [53] Wall K P, Pagratis M, Armstrong G, Balsbaugh J L, Verbeke E, Pearson C G and Hough L E 2016 ACS Chem. Biol. 11 2981 [54] Luchko T, Huzil J T, Stepanova M and Tuszynski J 2008 Biophys. J. 94 1971 [55] Jorgensen W, Chandrasekhar J, Madura J, Impey W and Klein M 1983 J. Chem. Phys. 79 926 [56] Phillips J, Braun R,WangW, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel R, Kale L and Schulten K 2005 J. Comput. Chem. 26 1781 [57] Humphrey W, Dalke A and Schulten K 1996 J. Mol. Graph. 14 33 [58] MacKerell A D, Bashford D, Bellott M, et al. 1998 J. Phys. Chem. B 102 3586 [59] Best R B, Zhu X, Shim J, Lopes P E M, Mittal J, FeigMand Mackerell A D 2012 J. Chem. Theory. Comput. 8 3257 [60] MacKerell A D, Feig M and Brooks C L 2004 J. Am. Chem. Soc. 126 698 [61] Pavelites J, Gao J, Bash P and MacKerell A 1997 J. Comput. Chem. 18 221 [62] Pan Z, Chen J, Lü G, Geng Y Z, Zhang H and Ji Q 2012 J. Chem. Phys. 136 164313 [63] Bai Q, Tan S, Xu T, Liu H, Huang J and Yao X 2021 Brief Bioinform. 22 bbaa161 [64] Prota A E, Bargsten K, Zurwerra D, Field J J, Díaz J F, Altmann K H and Steinmetz M O 2013 Science 339 587 [65] Beckett D and Voth G A 2023 Proc. Natl. Acad. Sci. USA 120 e2305898120 [66] Xie P 2024 Euro. Biophys. J. 53 339 [67] Xie P 2024 Adv. Protein Chem. Struct. Biol. 141 87
Altmetric calculates a score based on the online attention an article receives. Each coloured thread in the circle represents a different type of online attention. The number in the centre is the Altmetric score. Social media and mainstream news media are the main sources that calculate the score. Reference managers such as Mendeley are also tracked but do not contribute to the score. Older articles often score higher because they have had more time to get noticed. To account for this, Altmetric has included the context data for other articles of a similar age.
