Citation: Zhang Changsheng, Lai Luhua. Physiochemical Mechanisms of Biomolecular Liquid-Liquid Phase Separation[J]. Acta Physico-Chimica Sinica, ;2020, 36(1): 190705. doi: 10.3866/PKU.WHXB201907053 shu

Physiochemical Mechanisms of Biomolecular Liquid-Liquid Phase Separation

  • Corresponding author: Zhang Changsheng, changshengzhang@pku.edu.cn Lai Luhua, lhlai@pku.edu.cn
  • Received Date: 19 July 2019
    Revised Date: 9 September 2019
    Accepted Date: 10 September 2019
    Available Online: 24 January 2019

    Fund Project: the National Key Research and Development Program of China 2016YFA0502303The project was supported by the National Key Research and Development Program of China (2016YFA0502303) and the National Natural Science Foundation of China (21633001)the National Natural Science Foundation of China 21633001

  • The discoveries about the functions of biomolecular liquid-liquid phase separation in cell have been increased rapidly in the past decade. Condensates produced by phase separation play key roles in many cellular curial events. These biological functions are based on the physicochemical properties of phase separation. This review discusses the recent progress in understanding the physical and chemical mechanisms of biological liquid-liquid phase separation. (1) We summarized the basic properties and experimental characterization methods of phase separation droplets, including the morphology, fusion, and wetting, along with the dynamic properties of molecules in droplets, which are usually described by diffusion coefficients or viscosity and permeability. (2) We discussed the conditions affecting the liquid-liquid phase separation of biological molecules, including concentration, temperature, ionic strength, pH, and crowding effects. A database for liquid-liquid phase separation, LLPSDB, was introduced, and three types of nucleic acid concentration effects on the phase separation of protein molecules are discussed. These effects depend on the relative interaction strengths of protein-nucleic acid and protein-protein interactions. The major driving force of phase separation is multivalent interactions, and molecular flexibility is necessary for the dynamic properties. We summarized the diverse sources of multivalence, including multiple tandem repetitive domains, regular oligomerization, low-complexity domains (usually intrinsically disordered with repeat motifs for binding), and nucleic acid molecules via the main chain phosphates or repeat sequences. (3) We reviewed the statistical thermodynamics theories for describing the macromolecular liquid-liquid separation, including the Flory-Huggins theory, Overbeek-Voorn correction, random phase approximation method, and field theory simulation method. We discussed the experimental and simulation methods for studying the physiochemical mechanism of liquid-liquid phase separation. Model systems with simplified sequences for experimental studies were listed, including systems for studying the effects of charge properties, residue types, sequence length, and other properties. Molecular simulation methods can provide detailed information regarding the liquid-liquid phase separation process. We introduced two coarse-grain methods, the slab molecular dynamic simulation and Monte Carlo simulation using the lattice model. (4) The physiochemical properties of liquid-liquid phase separation govern the diverse functions of reversible phase transitions in a cell. We collected and analyzed important cases of biomolecular phase separation in cell activities. These biological functions were classified into five categories, including enrichment, sequestration, biological switching cooperation, localization, and mechanical force generation. We linked these functions with the physiochemical properties of liquid-liquid phase separation. To understand the specific phase-separation processes in biological activities, three types of related molecules must be studied: scaffold molecules mainly contributing to aggregate formation, recruited functional client molecules, and molecules that regulate the formation and disassembly of aggregates. We reviewed four regulation methods for the phase separation process, including changing the charge distribution by post-translational modification, changing the molecular concentration by gene expression or degradation regulation, changing the oligomerization state, and changing the cell solution environment (such as pH). Designing compounds for phase separation regulation has attracted significant attention for treating related diseases. Methods for discovering molecules that can regulate post-translational modifications or inhibit interactions in the droplets are emerging. The recently discovered phase separation phenomena and molecules in living organisms represent only the tip of the iceberg. In the future, it will be necessary to systematically examine liquid-liquid phase separation events and related molecules in all phases of biological processes.
  • 加载中
    1. [1]

      Dolgin, E. Nature 2018, 555 (7696), 300. doi: 10.1038/d41586-018-03070-2  doi: 10.1038/d41586-018-03070-2

    2. [2]

      Brangwynne, C. P.; Eckmann, C. R.; Courson, D. S.; Rybarska, A.; Hoege, C.; Gharakhani, J.; Julicher, F.; Hyman, A. A. Science 2009, 324 (5935), 1729. doi: 10.1126/science.1172046  doi: 10.1126/science.1172046

    3. [3]

      Franzmann, T. M.; Jahnel, M.; Pozniakovsky, A.; Mahamid, J.; Holehouse, A. S.; Nuske, E.; Richter, D.; Baumeister, W.; Grill, S. W.; Pappu, R. V.; et al. Science 2018, 359 (6371), 47. doi: 10.1126/science.aao5654  doi: 10.1126/science.aao5654

    4. [4]

      Sabari, B. R.; Dall'Agnese, A.; Boija, A.; Klein, I. A.; Coffey, E. L.; Shrinivas, K.; Abraham, B. J.; Hannett, N. M.; Zamudio, A. V.; Manteiga, J. C.; et al. Science 2018, 361 (6400), 379. doi: 10.1126/science.aar3958  doi: 10.1126/science.aar3958

    5. [5]

      Boija, A.; Klein, I. A.; Sabari, B. R.; Dall'Agnese, A.; Coffey, E. L.; Zamudio, A. V.; Li, C. H.; Shrinivas, K.; Manteiga, J. C.; Hannett, N. M.; Abraham, B. J.; et al. Cell 2018, 175 (7), 1842. doi: 10.1016/j.cell.2018.10.042  doi: 10.1016/j.cell.2018.10.042

    6. [6]

      Kilic, S.; Lezaja, A.; Gatti, M.; Bianco, E.; Michelena, J.; Imhof, R.; Altmeyer, M. EMBO J. 2019, e101379. doi: 10.15252/embj.2018101379  doi: 10.15252/embj.2018101379

    7. [7]

      Rai, A. K.; Chen, J. X.; Selbach, M.; Pelkmans, L. Nature 2018, 559 (7713), 211. doi: 10.1038/s41586-018-0279-8  doi: 10.1038/s41586-018-0279-8

    8. [8]

      Ryan, V. H.; Dignon, G. L.; Zerze, G. H.; Chabata, C. V.; Silva, R.; Conicella, A. E.; Amaya, J.; Burke, K. A.; Mittal, J.; Fawzi, N. L. Mol. Cell 2018, 69 (3), 465. doi: 10.1016/j.molcel.2017.12.022  doi: 10.1016/j.molcel.2017.12.022

    9. [9]

      Sear, R. P. Soft Matter 2007, 3 (6), 680. doi: 10.1039/b618126k  doi: 10.1039/b618126k

    10. [10]

      Su, X.; Ditlev, J. A.; Hui, E.; Xing, W.; Banjade, S.; Okrut, J.; King, D. S.; Taunton, J.; Rosen, M. K.; Vale, R. D. Science 2016, 352 (6285), 595. doi: 10.1126/science.aad9964  doi: 10.1126/science.aad9964

    11. [11]

      Du, M.; Chen, Z. J. Science 2018, 361 (6403), 704. doi: 10.1126/science.aat1022  doi: 10.1126/science.aat1022

    12. [12]

      Milovanovic, D.; Wu, Y.; Bian, X.; De Camilli, P. Science 2018, 361 (6402), 604. doi: 10.1126/science.aat5671  doi: 10.1126/science.aat5671

    13. [13]

      Gomes, E.; Shorter, J. J. Biol. Chem. 2019, 294 (18), 7115. doi: 10.1074/jbc.TM118.001192  doi: 10.1074/jbc.TM118.001192

    14. [14]

      Alberti, S.; Gladfelter, A.; Mittag, T. Cell 2019, 176 (3), 419. doi: 10.1016/j.cell.2018.12.035  doi: 10.1016/j.cell.2018.12.035

    15. [15]

      Boeynaems, S.; Holehouse, A. S.; Weinhardt, V.; Kovacs, D.; Van Lindt, J.; Larabell, C.; Van Den Bosch, L.; Das, R.; Tompa, P. S.; Pappu, R. V.; et al. Proc. Natl. Acad. Sci. U.S.A. 2019, 116 (16), 7889. doi: 10.1073/pnas.1821038116  doi: 10.1073/pnas.1821038116

    16. [16]

      Amiram, M.; Quiroz, F. G.; Callahan, D. J.; Chilkoti, A. Nat. Mater. 2011, 10 (2), 141. doi: 10.1038/nmat2942  doi: 10.1038/nmat2942

    17. [17]

      Stroberg, W.; Schnell, S. J. Theor. Biol. 2017, 434, 42. doi: 10.1016/j.jtbi.2017.04.006  doi: 10.1016/j.jtbi.2017.04.006

    18. [18]

      Shayegan, M.; Tahvildari, R.; Metera, K.; Kisley, L.; Michnick, S. W.; Leslie, S. R. J. Am. Chem. Soc. 2019, 141 (19), 7751. doi: 10.1021/jacs.8b13349  doi: 10.1021/jacs.8b13349

    19. [19]

      Wang, J.; Choi, J. M.; Holehouse, A. S.; Lee, H. O.; Zhang, X.; Jahnel, M.; Maharana, S.; Lemaitre, R.; Pozniakovsky, A.; Drechsel, D.; et al. Cell 2018, 174 (3), 688. doi: 10.1016/j.cell.2018.06.006  doi: 10.1016/j.cell.2018.06.006

    20. [20]

      Patel, A.; Lee, H. O.; Jawerth, L.; Maharana, S.; Jahnel, M.; Hein, M. Y.; Stoynov, S.; Mahamid, J.; Saha, S.; Franzmann, T. M.; et al. Cell 2015, 162 (5), 1066. doi: 10.1016/j.cell.2015.07.047  doi: 10.1016/j.cell.2015.07.047

    21. [21]

      Brangwynne, C. P.; Mitchison, T. J.; Hyman, A. A. Proc. Natl. Acad. Sci. U.S.A. 2011, 108 (11), 4334. doi: 10.1073/pnas.1017150108  doi: 10.1073/pnas.1017150108

    22. [22]

      Eggers, J.; Lister, J. R.; Stone, H. A. J. Fluid Mech. 1999, 401, 293. doi: 10.1017/s002211209900662x  doi: 10.1017/s002211209900662x

    23. [23]

      Berry, J.; Weber, S. C.; Vaidya, N.; Haataja, M.; Brangwynne, C. P. Proc. Natl. Acad. Sci. U.S.A. 2015, 112 (38), E5237. doi: 10.1073/pnas.1509317112  doi: 10.1073/pnas.1509317112

    24. [24]

      Shin, Y.; Brangwynne, C. P. Science 2017, 357 (6357). doi: 10.1126/science.aaf4382  doi: 10.1126/science.aaf4382

    25. [25]

      Feric, M.; Vaidya, N.; Harmon, T. S.; Mitrea, D. M.; Zhu, L.; Richardson, T. M.; Kriwacki, R. W.; Pappu, R. V.; Brangwynne, C. P. Cell 2016, 165 (7), 1686. doi: 10.1016/j.cell.2016.04.047  doi: 10.1016/j.cell.2016.04.047

    26. [26]

      Wei, M. T.; Elbaum-Garfinkle, S.; Holehouse, A. S.; Chen, C. C. H.; Feric, M.; Arnold, C. B.; Priestley, R. D.; Pappu, R. V.; Brangwynne, C. P. Nat. Chem. 2017, 9 (11), 1118. doi: 10.1038/nchem.2803  doi: 10.1038/nchem.2803

    27. [27]

      Brady, J. P.; Farber, P. J.; Sekhar, A.; Lin, Y. H.; Huang, R.; Bah, A.; Nott, T. J.; Chan, H. S.; Baldwin, A. J.; Forman-Kay, J. D.; et al. Proc. Natl. Acad. Sci. U.S.A. 2017, 114 (39), E8194. doi: 10.1073/pnas.1706197114  doi: 10.1073/pnas.1706197114

    28. [28]

      Reichheld, S. E.; Muiznieks, L. D.; Keeley, F. W.; Sharpe, S. Proc. Natl. Acad. Sci. U.S.A. 2017, 114 (22), E4408. doi: 10.1073/pnas.1701877114  doi: 10.1073/pnas.1701877114

    29. [29]

      Schuster, B. S.; Reed, E. H.; Parthasarathy, R.; Jahnke, C. N.; Caldwell, R. M.; Bermudez, J. G.; Ramage, H.; Good, M. C.; Hammer, D. A. Nat. Commun. 2018, 9, 2985. doi: 10.1038/s41467-018-05403-1  doi: 10.1038/s41467-018-05403-1

    30. [30]

      Muiznieks, L. D.; Keeley, F. W. J. Biol. Chem. 2010, 285 (51), 39779. doi: 10.1074/jbc.M110.164467  doi: 10.1074/jbc.M110.164467

    31. [31]

      Ambadipudi, S.; Biernat, J.; Riedel, D.; Mandelkow, E.; Zweckstetter, M. Nat. Commun. 2017, 8, 275. doi: 10.1038/s41467-017-00480-0  doi: 10.1038/s41467-017-00480-0

    32. [32]

      Burke, K. A.; Janke, A. M.; Rhine, C. L.; Fawzi, N. L. Mol. Cell 2015, 60 (2), 231. doi: 10.1016/j.molcel.2015.09.006  doi: 10.1016/j.molcel.2015.09.006

    33. [33]

      Langdon, E. M.; Qiu, Y.; Niaki, A. G.; McLaughlin, G. A.; Weidmann, C. A.; Gerbich, T. M.; Smith, J. A.; Crutchley, J. M.; Termini, C. M.; Weeks, K. M.; et al. Science 2018, 360 (6391), 922. doi: 10.1126/science.aar7432  doi: 10.1126/science.aar7432

    34. [34]

      Cho, E. J.; Kim, J. S. J. Phys. Chem. B 2012, 116 (12), 3874. doi: 10.1021/jp3006525  doi: 10.1021/jp3006525

    35. [35]

      Banerjee, P. R.; Milin, A. N.; Moosa, M. M.; Onuchic, P. L.; Deniz, A. A. Angew. Chem. Int. Ed. 2017, 56 (38), 11354. doi: 10.1002/anie.201703191  doi: 10.1002/anie.201703191

    36. [36]

      Nguemaha, V.; Zhou, H. X. Sci. Rep. 2018, 8, 6728. doi: 10.1038/s41598-018-25132-1  doi: 10.1038/s41598-018-25132-1

    37. [37]

      Panagiotopoulos, A. Z. Mol. Phys. 1987, 61 (4), 813. doi: 10.1080/00268978700101491  doi: 10.1080/00268978700101491

    38. [38]

      Kern, N.; Frenkel, D. J. Chem. Phys. 2003, 118 (21), 9882. doi: 10.1063/1.1569473  doi: 10.1063/1.1569473

    39. [39]

      Li, Q.; Peng, X.; Li, Y.; Tang, W.; Zhu, J.; Huang, J.; Qi, Y.; Zhang, Z. Nucleic Acids Res. 2019. Online publication date: 6-Sep-2019. doi: 10.1093/nar/gkz778

    40. [40]

      Wu, R. B.; Li, P. L. Chin. Sci. Bull. 2019, 64.doi: 10.1360/N972019-00281  doi: 10.1360/N972019-00281

    41. [41]

      Banani, S. F.; Lee, H. O.; Hyman, A. A.; Rosen, M. K. Nat. Rev. Mol. Cell Biol. 2017, 18 (5), 285. doi: 10.1038/nrm.2017.7  doi: 10.1038/nrm.2017.7

    42. [42]

      Li, P.; Banjade, S.; Cheng, H. C.; Kim, S.; Chen, B.; Guo, L.; Llaguno, M.; Hollingsworth, J. V.; King, D. S.; Banani, S. F.; et al. Nature 2012, 483 (7389), 336. doi: 10.1038/nature10879  doi: 10.1038/nature10879

    43. [43]

      Sun, D.; Wu, R.; Zheng, J.; Li, P.; Yu, L. Cell Res. 2018, 28 (4), 405. doi: 10.1038/s41422-018-0017-7  doi: 10.1038/s41422-018-0017-7

    44. [44]

      Zeng, M.; Shang, Y.; Araki, Y.; Guo, T.; Huganir, R. L.; Zhang, M. Cell 2016, 166 (5), 1163. doi: 10.1016/j.cell.2016.07.008  doi: 10.1016/j.cell.2016.07.008

    45. [45]

      Martin, E. W.; Mittag, T. Biochemistry 2018, 57 (17), 2478. doi: 10.1021/acs.biochem.8b00008  doi: 10.1021/acs.biochem.8b00008

    46. [46]

      Uversky, V. N. Curr. Opin. Struct. Biol. 2017, 44, 18. doi: 10.1016/j.sbi.2016.10.015  doi: 10.1016/j.sbi.2016.10.015

    47. [47]

      Nott, T. J.; Petsalaki, E.; Farber, P.; Jervis, D.; Fussner, E.; Plochowietz, A.; Craggs, T. D.; Bazett-Jones, D. P.; Pawson, T.; Forman-Kay, J. D.; et al. Mol. Cell 2015, 57 (5), 936. doi: 10.1016/j.molcel.2015.01.013  doi: 10.1016/j.molcel.2015.01.013

    48. [48]

      Lin, Y. H.; Forman-Kay, J. D.; Chan, H. S. Phys. Rev. Lett. 2016, 117 (17), 178101. doi: 10.1103/PhysRevLett.117.178101  doi: 10.1103/PhysRevLett.117.178101

    49. [49]

      Vernon, R. M.; Chong, P. A.; Tsang, B.; Kim, T. H.; Bah, A.; Farber, P.; Lin, H.; Forman-Kay, J. D. Elife 2018, 7, e31486. doi: 10.7554/eLife.31486  doi: 10.7554/eLife.31486

    50. [50]

      Escobedo, A.; Topal, B.; Kunze, M. B. A.; Aranda, J.; Chiesa, G.; Mungianu, D.; Bernardo-Seisdedos, G.; Eftekharzadeh, B.; Gairi, M.; Pierattelli, R.; et al. Nat. Commun. 2019, 10, 2034. doi: 10.1038/s41467-019-09923-2  doi: 10.1038/s41467-019-09923-2

    51. [51]

      Sawaya, M. R.; Sambashivan, S.; Nelson, R.; Ivanova, M. I.; Sievers, S. A.; Apostol, M. I.; Thompson, M. J.; Balbirnie, M.; Wiltzius, J. J. W.; McFarlane, H. T.; et al. Nature 2007, 447 (7143), 453. doi: 10.1038/nature05695  doi: 10.1038/nature05695

    52. [52]

      Peskett, T. R.; Rau, F.; O'Driscoll, J.; Patani, R.; Lowe, A. R.; Saibil, H. R. Mol. Cell 2018, 70 (4), 588. doi: 10.1016/j.molcel.2018.04.007  doi: 10.1016/j.molcel.2018.04.007

    53. [53]

      Fiumara, F.; Fioriti, L.; Kandel, E. R.; Hendrickson, W. A. Cell 2010, 143 (7), 1121. doi: 10.1016/j.cell.2010.11.042  doi: 10.1016/j.cell.2010.11.042

    54. [54]

      Vieregg, J. R.; Lueckheide, M.; Marciel, A. B.; Leon, L.; Bologna, A. J.; Rivera, J. R.; Tirrell, M. V. J. Am. Chem. Soc. 2018, 140 (5), 1632. doi: 10.1021/jacs.7b03567  doi: 10.1021/jacs.7b03567

    55. [55]

      Jain, A.; Vale, R. D. Nature 2017, 546 (7657), 243. doi: 10.1038/nature22386  doi: 10.1038/nature22386

    56. [56]

      Zhang, H.; Elbaum-Garfinkle, S.; Langdon, E. M.; Taylor, N.; Occhipinti, P.; Bridges, A. A.; Brangwynne, C. P.; Gladfelter, A. S. Mol. Cell 2015, 60 (2), 220. doi: 10.1016/j.molcel.2015.09.017  doi: 10.1016/j.molcel.2015.09.017

    57. [57]

      Brangwynne, C. P.; Tompa, P.; Pappu, R. V. Nat. Phys. 2015, 11 (11), 899. doi: 10.1038/nphys3532  doi: 10.1038/nphys3532

    58. [58]

      Flory, P. J. J. Chem. Phys. 1942, 10 (1), 51. doi: 10.1063/1.1723621  doi: 10.1063/1.1723621

    59. [59]

      Huggins, M. L. J.Phys. Chem. 1942, 46 (1), 151. doi: 10.1021/ j150415a018  doi: 10.1021/j150415a018

    60. [60]

      Zhou, H. X.; Nguemaha, V.; Mazarakos, K.; Qin, S. Trends Biochem. Sci. 2018, 43 (7), 499. doi: 10.1016/j.tibs.2018.03.007  doi: 10.1016/j.tibs.2018.03.007

    61. [61]

      Overbeek, J. T.; Voorn, M. J. J. Cell. Physiol. Supplement 1957, 49 (Suppl 1), 7. doi: 10.1002/jcp.1030490404  doi: 10.1002/jcp.1030490404

    62. [62]

      Wittmer, J.; Johner, A.; Joanny, J. F. Europhys. Lett. 1993, 24 (4), 263. doi: 10.1209/0295-5075/24/4/005  doi: 10.1209/0295-5075/24/4/005

    63. [63]

      Borue, V. Y.; Erukhimovich, I. Y. Macromolecules 1988, 21 (11), 3240. doi: 10.1021/ma00189a019  doi: 10.1021/ma00189a019

    64. [64]

      Lin, Y. H.; Brady, J. P.; Forman-Kay, J. D.; Chan, H. S. New J. Phys. 2017, 19, 115003. doi: 10.1088/1367-2630/aa9369  doi: 10.1088/1367-2630/aa9369

    65. [65]

      McCarty, J.; Delaney, K. T.; Danielsen, S. P. O.; Fredrickson, G. H.; Shea, J. E. J. Phys. Chem. Lett. 2019, 10 (8), 1644. doi: 10.1021/acs.jpclett.9b00099  doi: 10.1021/acs.jpclett.9b00099

    66. [66]

      Banjade, S.; Wu, Q.; Mittal, A.; Peeples, W. B.; Pappu, R. V.; Rosen, M. K. Proc. Natl. Acad. Sci. U.S.A. 2015, 112 (47), E6426. doi: 10.1073/pnas.1508778112  doi: 10.1073/pnas.1508778112

    67. [67]

      Quiroz, F. G.; Chilkoti, A. Nat. Mater. 2015, 14 (11), 1164. doi: 10.1038/nmat4418  doi: 10.1038/nmat4418

    68. [68]

      Zhou, H.; Song, Z.; Zhong, S.; Zuo, L.; Qi, Z.; Qu, L. J.; Lai, L. Angew. Chem. Int. Ed. 2019, 58 (15), 4858. doi: 10.1002/anie.201810373  doi: 10.1002/anie.201810373

    69. [69]

      Chang, L. W.; Lytle, T. K.; Radhakrishna, M.; Madinya, J. J.; Velez, J.; Sing, C. E.; Perry, S. L. Nat. Commun. 2017, 8, 1273. doi: 10.1038/s41467-017-01249-1  doi: 10.1038/s41467-017-01249-1

    70. [70]

      Dignon, G. L.; Zheng, W.; Mittal, J. Curr. Opin. Chem. Eng. 2019, 23, 92. doi: 10.1016/j.coche.2019.03.004  doi: 10.1016/j.coche.2019.03.004

    71. [71]

      Dignon, G. L.; Zheng, W.; Kim, Y. C.; Best, R. B.; Mittal, J. Plos Comput. Biol. 2018, 14 (1), e1005941. doi: 10.1371/journal.pcbi.1005941  doi: 10.1371/journal.pcbi.1005941

    72. [72]

      Choi, J. M.; Dar, F.; Pappu, R. V. bioRxiv 2019, 611095. doi: 10.1101/611095  doi: 10.1101/611095

    73. [73]

      Das, S.; Eisen, A.; Lin, Y. H.; Chan, H. S. J. Phys. Chem. B 2018, 122 (21), 5418. doi: 10.1021/acs.jpcb.7b11723  doi: 10.1021/acs.jpcb.7b11723

    74. [74]

      Das, S.; Amin, A. N.; Lin, Y. H.; Chan, H. S. Phys. Chem. Chem. Phys. 2018, 20 (45), 28558. doi: 10.1039/c8cp05095c  doi: 10.1039/c8cp05095c

    75. [75]

      Dignon, G. L.; Zheng, W.; Best, R. B.; Kim, Y. C.; Mittal, J. Proc. Natl. Acad. Sci. U.S.A. 2018, 115 (40), 9929. doi: 10.1073/pnas.1804177115  doi: 10.1073/pnas.1804177115

    76. [76]

      Harmon, T. S.; Holehouse, A. S.; Rosen, M. K.; Pappu, R. V. Elife 2017, 6, e30294. doi: 10.7554/eLife.30294  doi: 10.7554/eLife.30294

    77. [77]

      Mitrea, D. M.; Kriwacki, R. W. Cell Commun. Signal. 2016, 14, 1. doi: 10.1186/s12964-015-0125-7  doi: 10.1186/s12964-015-0125-7

    78. [78]

      Strulson, C. A.; Molden, R. C.; Keating, C. D.; Bevilacqua, P. C. Nat. Chem. 2012, 4 (11), 941. doi: 10.1038/nchem.1466  doi: 10.1038/nchem.1466

    79. [79]

      Case, L. B.; Zhang, X.; Ditlev, J. A.; Rosen, M. K. Science 2019, 363 (6431), 1093. doi: 10.1126/science.aau6313  doi: 10.1126/science.aau6313

    80. [80]

      Riback, J. A.; Katanski, C. D.; Kear-Scott, J. L.; Pilipenko, E. V.; Rojek, A. E.; Sosnick, T. R.; Drummond, D. A. Cell 2017, 168 (6), 1028. doi: 10.1016/j.cell.2017.02.027  doi: 10.1016/j.cell.2017.02.027

    81. [81]

      Altmeyer, M.; Neelsen, K. J.; Teloni, F.; Pozdnyakova, I.; Pellegrino, S.; Grofte, M.; Rask, M. B. D.; Streicher, W.; Jungmichel, S.; Nielsen, M. L.; et al. Nat. Commun. 2015, 6, 8088. doi: 10.1038/ncomms9088  doi: 10.1038/ncomms9088

    82. [82]

      Hnisz, D.; Shrinivas, K.; Young, R. A.; Chakraborty, A. K.; Sharp, P. A. Cell 2017, 169 (1), 13. doi: 10.1016/j.cell.2017.02.007  doi: 10.1016/j.cell.2017.02.007

    83. [83]

      Wang, J. T. f.; Smith, J.; Chen, B. C.; Schmidt, H.; Rasoloson, D.; Paix, A.; Lambrus, B. G.; Calidas, D.; Betzig, E.; Seydoux, G. Elife 2014, 3, e04591. doi: 10.7554/eLife.04591  doi: 10.7554/eLife.04591

    84. [84]

      Smith, J.; Calidas, D.; Schmidt, H.; Lu, T.; Rasoloson, D.; Seydoux, G. Elife 2016, 5, e21337. doi: 10.7554/eLife.21337  doi: 10.7554/eLife.21337

    85. [85]

      Zhang, G.; Wang, Z.; Du, Z.; Zhang, H. Cell 2018, 174 (6), 1492. doi: 10.1016/j.cell.2018.08.006  doi: 10.1016/j.cell.2018.08.006

    86. [86]

      Li, S.; Yang, P.; Tian, E.; Zhang, H. Mol. Cell 2013, 52 (3), 421. doi: 10.1016/j.molcel.2013.09.014  doi: 10.1016/j.molcel.2013.09.014

    87. [87]

      Boczek, E. E.; Alberti, S. Science 2018, 361 (6402), 548. doi: 10.1126/science.aau5477  doi: 10.1126/science.aau5477

    88. [88]

      Wippich, F.; Bodenmiller, B.; Trajkovska, M. G.; Wanka, S.; Aebersold, R.; Pelkmans, L. Cell 2013, 152 (4), 791. doi: 10.1016/j.cell.2013.01.033  doi: 10.1016/j.cell.2013.01.033

    89. [89]

      Zacharogianni, M.; Gomez, A. A.; Veenendaal, T.; Smout, J.; Rabouille, C. Elife 2014, 3, e04132. doi: 10.7554/eLife.04132  doi: 10.7554/eLife.04132

    90. [90]

      van Leeuwen, W.; van der Krift, F.; Rabouille, C. J. Cell Biol. 2018, 217 (7), 2261. doi: 10.1083/jcb.201802003  doi: 10.1083/jcb.201802003

    91. [91]

      Shin, Y.; Chang, Y. C.; Lee, D. S. W.; Berry, J.; Sanders, D. W.; Ronceray, P.; Wingreen, N. S.; Haataja, M.; Brangwynne, C. P. Cell 2018, 175 (6), 1481. doi: 10.1016/j.cell.2018.10.057  doi: 10.1016/j.cell.2018.10.057

    92. [92]

      Larson, A. G.; Elnatan, D.; Keenen, M. M.; Trnka, M. J.; Ohnston, J. B. J.; Burlingame, A. L.; Agard, D. A.; Redding, S.; Narlikar, G. J. Nature 2017, 547 (7662), 236. doi: 10.1038/nature22822  doi: 10.1038/nature22822

    93. [93]

      Lu, H.; Yu, D.; Hansen, A. S.; Ganguly, S.; Liu, R.; Heckert, A.; Darzacq, X.; Zhou, Q. Nature 2018, 558 (7709), 318. doi: 10.1038/s41586-018-0174-3  doi: 10.1038/s41586-018-0174-3

    94. [94]

      Harlen, K. M.; Churchman, L. S. Nat. Rev. Mol. Cell Biol. 2017, 18 (4), 263. doi: 10.1038/nrm.2017.10  doi: 10.1038/nrm.2017.10

    95. [95]

      Fang, X.; Wang, L.; Ishikawa, R.; Li, Y.; Fiedler, M.; Liu, F.; Calder, G.; Rowan, B.; Weigel, D.; Li, P.; Dean, C. Nature 2019, 569 (7755), 265. doi: 10.1038/s41586-019-1165-8  doi: 10.1038/s41586-019-1165-8

    96. [96]

      Ferrolino, M. C.; Mitrea, D. M.; Michael, J. R.; Kriwacki, R. W. Nat. Commun. 2018, 9, 5064. doi: 10.1038/s41467-018-07530-1  doi: 10.1038/s41467-018-07530-1

    97. [97]

      Jiang, H.; Wang, S.; Huang, Y.; He, X.; Cui, H.; Zhu, X.; Zheng, Y. Cell 2015, 163 (1), 108. doi: 10.1016/j.cell.2015.08.010  doi: 10.1016/j.cell.2015.08.010

    98. [98]

      Woodruff, J. B. J. Mol. Biol. 2018, 430 (23), 4762. doi: 10.1016/j.jmb.2018.04.041  doi: 10.1016/j.jmb.2018.04.041

    99. [99]

      Bergeron-Sandoval, L. P.; Heris, H. K.; Hendricks, A. G.; Ehrlicher, A. J.; Franois, P.; Pappu, R. V.; Michnick, S. W. bioRxiv 2017, 145664. doi: 10.1101/145664  doi: 10.1101/145664

    100. [100]

      Saito, M.; Hess, D.; Eglinger, J.; Fritsch, A. W.; Kreysing, M.; Weinert, B. T.; Choudhary, C.; Matthias, P. Nat. Chem. Biol. 2019, 15 (1), 51. doi: 10.1038/s41589-018-0180-7  doi: 10.1038/s41589-018-0180-7

    101. [101]

      Patel, A.; Malinovska, L.; Saha, S.; Wang, J.; Alberti, S.; Krishnan, Y.; Hyman, A. A. Science 2017, 356 (6339), 753. doi: 10.1126/science.aaf6846  doi: 10.1126/science.aaf6846

    102. [102]

      Aumiller, W. M., Jr.; Keating, C. D. Nat. Chem. 2016, 8 (2), 129. doi: 10.1038/nchem.2414  doi: 10.1038/nchem.2414

    103. [103]

      Cermakova, K.; Hodges, H. C. Molecules 2018, 23 (8), 1958. doi: 10.3390/molecules23081958  doi: 10.3390/molecules23081958

    104. [104]

      McGurk, L.; Gomes, E.; Guo, L.; Mojsilovic-Petrovic, J.; Tran, V.; Kalb, R. G.; Shorter, J.; Bonini, N. M. Mol. Cell 2018, 71 (5), 703. doi: 10.1016/j.molcel.2018.07.002  doi: 10.1016/j.molcel.2018.07.002

    105. [105]

      Jin, F.; Yu, C.; Lai, L.; Liu, Z. Plos Comput. Biol. 2013, 9 (10), e1003249. doi: 10.1371/journal.pcbi.1003249  doi: 10.1371/journal.pcbi.1003249

    106. [106]

      Yu, C.; Niu, X.; Jin, F.; Liu, Z.; Jin, C.; Lai, L. Sci. Rep. 2016, 6, 22298. doi: 10.1038/srep22298  doi: 10.1038/srep22298

    107. [107]

      Fang, M. Y.; Markmiller, S.; Vu, A. Q.; Javaherian, A.; Dowdle, W. E.; Jolivet, P.; Bushway, P. J.; Castello, N. A.; Baral, A.; Chan, M. Y.; et al. Neuron 2019, 5, 802, doi: 10.1016/j.neuron.2019.05.048  doi: 10.1016/j.neuron.2019.05.048

    108. [108]

      Warshel, A.; Kato, M.; Pisliakov, A. V. J. Chem. Theory Comput. 2007, 3 (6), 2034. doi: 10.1021/ct700127w  doi: 10.1021/ct700127w

    109. [109]

      Ponder, J. W.; Wu, C.; Ren, P.; Pande, V. S.; Chodera, J. D.; Schnieders, M. J.; Haque, I.; Mobley, D. L.; Lambrecht, D. S.; DiStasio, R. A., et al. J. Phys. Chem. B 2010, 114 (8), 2549. doi: 10.1021/jp910674d  doi: 10.1021/jp910674d

    110. [110]

      Zhang, C.; Bell, D.; Harger, M.; Ren, P. J. Chem. Theory Comput. 2017, 13 (2), 666. doi: 10.1021/acs.jctc.6b00918  doi: 10.1021/acs.jctc.6b00918

    111. [111]

      Ruan, H.; Sun, Q.; Zhang, W.; Liu, Y.; Lai, L. Drug Discov. Today 2019, 24 (1), 217. doi: 10.1016/j.drudis.2018.09.017  doi: 10.1016/j.drudis.2018.09.017

  • 加载中
    1. [1]

      Xinyi Hong Tailing Xue Zhou Xu Enrong Xie Mingkai Wu Qingqing Wang Lina Wu . Non-Site-Specific Fluorescent Labeling of Proteins as a Chemical Biology Experiment. University Chemistry, 2024, 39(4): 351-360. doi: 10.3866/PKU.DXHX202310010

    2. [2]

      Zijuan LIXuan LÜJiaojiao CHENHaiyang ZHAOShuo SUNZhiwu ZHANGJianlong ZHANGYanling MAJie LIZixian FENGJiahui LIU . Synthesis of visual fluorescence emission CdSe nanocrystals based on ligand regulation. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 308-320. doi: 10.11862/CJIC.20240138

    3. [3]

      Xinyu ZENGGuhua TANGJianming OUYANG . Inhibitory effect of Desmodium styracifolium polysaccharides with different content of carboxyl groups on the growth, aggregation and cell adhesion of calcium oxalate crystals. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1563-1576. doi: 10.11862/CJIC.20230374

    4. [4]

      Yaping Li Sai An Aiqing Cao Shilong Li Ming Lei . The Application of Molecular Simulation Software in Structural Chemistry Education: First-Principles Calculation of NiFe Layered Double Hydroxide. University Chemistry, 2025, 40(3): 160-170. doi: 10.12461/PKU.DXHX202405185

    5. [5]

      Pingping Zhu Yongjun Xie Yuanping Yi Yu Huang Qiang Zhou Shiyan Xiao Haiyang Yang Pingsheng He . Excavation and Extraction of Ideological and Political Elements for the Virtual Simulation Experiments at Molecular Level: Taking the Project “the Simulation and Computation of Conformation, Morphology and Dimensions of Polymer Chains” as an Example. University Chemistry, 2024, 39(2): 83-88. doi: 10.3866/PKU.DXHX202309063

    6. [6]

      Junjie Zhang Yue Wang Qiuhan Wu Ruquan Shen Han Liu Xinhua Duan . Preparation and Selective Separation of Lightweight Magnetic Molecularly Imprinted Polymers for Trace Tetracycline Detection in Milk. University Chemistry, 2024, 39(5): 251-257. doi: 10.3866/PKU.DXHX202311084

    7. [7]

      Jingwen Wang Minghao Wu Xing Zuo Yaofeng Yuan Yahao Wang Xiaoshun Zhou Jianfeng Yan . Advances in the Application of Electrochemical Regulation in Investigating the Electron Transport Properties of Single-Molecule Junctions. University Chemistry, 2025, 40(3): 291-301. doi: 10.12461/PKU.DXHX202406023

    8. [8]

      Shuang Meng Haixin Long Zhou Zhou Meizhu Rong . Inorganic Chemistry Curriculum Design and Implementation of Based on “Stepped-Task Driven + Multi-Dimensional Output” Model: A Case Study on Intermolecular Forces. University Chemistry, 2024, 39(3): 122-131. doi: 10.3866/PKU.DXHX202309008

    9. [9]

      Jiaxun Wu Mingde Li Li Dang . The R eaction of Metal Selenium Complexes with Olefins as a Tutorial Case Study for Analyzing Molecular Orbital Interaction Modes. University Chemistry, 2025, 40(3): 108-115. doi: 10.12461/PKU.DXHX202405098

    10. [10]

      Supin Zhao Jing Xie . Understanding the Vibrational Stark Effect of Water Molecules Using Quantum Chemistry Calculations. University Chemistry, 2025, 40(3): 178-185. doi: 10.12461/PKU.DXHX202406024

    11. [11]

      Jie ZHAOSen LIUQikang YINXiaoqing LUZhaojie WANG . Theoretical calculation of selective adsorption and separation of CO2 by alkali metal modified naphthalene/naphthalenediyne. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 515-522. doi: 10.11862/CJIC.20230385

    12. [12]

      Yanan Jiang Yuchen Ma . Brief Discussion on the Electronic Exchange Interaction in Quantum Chemistry Computations. University Chemistry, 2025, 40(3): 10-15. doi: 10.12461/PKU.DXHX202402058

    13. [13]

      Lan Ma Cailu He Ziqi Liu Yaohan Yang Qingxia Ming Xue Luo Tianfeng He Liyun Zhang . Magical Surface Chemistry: Fabrication and Application of Oil-Water Separation Membranes. University Chemistry, 2024, 39(5): 218-227. doi: 10.3866/PKU.DXHX202311046

    14. [14]

      Pei Li Yuenan Zheng Zhankai Liu An-Hui Lu . Boron-Containing MFI Zeolite: Microstructure Control and Its Performance of Propane Oxidative Dehydrogenation. Acta Physico-Chimica Sinica, 2025, 41(4): 100034-. doi: 10.3866/PKU.WHXB202406012

    15. [15]

      Yanyang Li Zongpei Zhang Kai Li Shuangquan Zang . Ideological and Political Design for the Comprehensive Experiment of the Synthesis and Aggregation-Induced Emission (AIE) Performance Study of Salicylaldehyde Schiff-Base. University Chemistry, 2024, 39(2): 105-109. doi: 10.3866/PKU.DXHX202307020

    16. [16]

      Peipei Sun Jinyuan Zhang Yanhua Song Zhao Mo Zhigang Chen Hui Xu . 引入内建电场增强光载流子分离以促进H2的生产. Acta Physico-Chimica Sinica, 2024, 40(11): 2311001-. doi: 10.3866/PKU.WHXB202311001

    17. [17]

      Jie ZHAOHuili ZHANGXiaoqing LUZhaojie WANG . Theoretical calculations of CO2 capture and separation by functional groups modified 2D covalent organic framework. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 275-283. doi: 10.11862/CJIC.20240213

    18. [18]

      Feiya Cao Qixin Wang Pu Li Zhirong Xing Ziyu Song Heng Zhang Zhibin Zhou Wenfang Feng . Magnesium-Ion Conducting Electrolyte Based on Grignard Reaction: Synthesis and Properties. University Chemistry, 2024, 39(3): 359-368. doi: 10.3866/PKU.DXHX202308094

    19. [19]

      Huiying Xu Minghui Liang Zhi Zhou Hui Gao Wei Yi . Application of Quantum Chemistry Computation and Visual Analysis in Teaching of Weak Interactions. University Chemistry, 2025, 40(3): 199-205. doi: 10.12461/PKU.DXHX202407011

    20. [20]

      Chunai Dai Yongsheng Han Luting Yan Zhen Li Yingze Cao . Ideological and Political Design of Solid-liquid Contact Angle Measurement Experiment. University Chemistry, 2024, 39(2): 28-33. doi: 10.3866/PKU.DXHX202306065

Metrics
  • PDF Downloads(13)
  • Abstract views(641)
  • HTML views(125)

通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索
Address:Zhongguancun North First Street 2,100190 Beijing, PR China Tel: +86-010-82449177-888
Powered By info@rhhz.net

/

DownLoad:  Full-Size Img  PowerPoint
Return