Predicting disordered regions driving phase separation of proteins under variable salt concentration

被引:2
|
作者
Meca, Esteban [1 ]
Fritsch, Anatol W. [2 ,3 ]
Iglesias-Artola, Juan M. [2 ]
Reber, Simone [4 ,5 ,6 ]
Wagner, Barbara [7 ]
机构
[1] Univ Cordoba, Dept Fis Aplicada Radiol & Med Fis, Cordoba, Spain
[2] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany
[3] Ctr Syst Biol Dresden, Dresden, Germany
[4] Humboldt Univ, IRI Life Sci, Berlin, Germany
[5] Max Planck Inst Infect Biol, Berlin, Germany
[6] Univ Appl Sci Berlin, Berlin, Germany
[7] Weierstrass Inst Berlin, Berlin, Germany
关键词
intrinsically disordered proteins (IDP); Random Phase Approximation (RPA); FUS; liquid-liquid phase separation (LLPS); phase diagrams; CHARGED POLYELECTROLYTES; COMPLEX COACERVATION; GRANULES;
D O I
10.3389/fphy.2023.1213304
中图分类号
O4 [物理学];
学科分类号
0702 ;
摘要
We investigate intrinsically disordered regions (IDRs) of phase separating proteins regarding their impact on liquid-liquid phase separation (LLPS) of the full protein. Our theoretical approach uses a mean-field theory that accounts for sequence-dependent electrostatic interactions via a Random Phase Approximation (RPA) and in addition allows for variable salt concentration for the condensed and dilute protein phases. The numerical solution of the complete phase diagrams together with the tie lines that we derive for this model system leaves two parameters to be determined by fitting experimental data on concentrations of all species involved in the system. For our comparisons, we focus on two proteins, PGL-3 and FUS, known to undergo LLPS. For PGL-3 we predict that its long IDR near the C-terminus promotes LLPS, which we validate through direct comparison with in vitro experimental results under the same physiological conditions. For the structurally more complex protein FUS the role of the low complexity (LC) domain in LLPS has been intensively studied. Apart from the LC domain we here investigate theoretically two IDRs, one near the N-terminus and another near the C-terminus. Our theoretical analysis of these domains predict that the IDR at the N-terminus (aa 1-285) is the main driver of LLPS of FUS by comparison to in vitro experiments of the full length protein under the same physiological temperature and salt conditions.
引用
收藏
页数:13
相关论文
共 50 条
  • [1] MemDis: Predicting Disordered Regions in Transmembrane Proteins
    Dobson, Laszlo
    Tusnady, Gabor E.
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (22)
  • [2] Phase Separation of Intrinsically Disordered Proteins
    Posey, Ammon E.
    Holehouse, Alex S.
    Pappu, Rohit V.
    INTRINSICALLY DISORDERED PROTEINS, 2018, 611 : 1 - 30
  • [3] Acetylation of intrinsically disordered regions regulates phase separation
    Makoto Saito
    Daniel Hess
    Jan Eglinger
    Anatol W. Fritsch
    Moritz Kreysing
    Brian T. Weinert
    Chunaram Choudhary
    Patrick Matthias
    Nature Chemical Biology, 2019, 15 : 51 - 61
  • [4] Acetylation of intrinsically disordered regions regulates phase separation
    Saito, Makoto
    Hess, Daniel
    Eglinger, Jan
    Fritsch, Anatol W.
    Kreysing, Moritz
    Weinert, Brian T.
    Choudhary, Chunaram
    Matthias, Patrick
    NATURE CHEMICAL BIOLOGY, 2019, 15 (01) : 51 - +
  • [5] Disordered regions as regulators of phase transitions in multivalent proteins
    Pappu, Rohit V.
    FASEB JOURNAL, 2018, 32 (01):
  • [6] How do intrinsically disordered protein regions encode a driving force for liquid-liquid phase separation?
    Borcherds, Wade
    Bremer, Anne
    Borgia, Madeleine B.
    Mittag, Tanja
    CURRENT OPINION IN STRUCTURAL BIOLOGY, 2021, 67 : 41 - 50
  • [7] Inducing phase separation using artificial disordered proteins
    Singh, Arunima
    NATURE METHODS, 2020, 17 (10) : 955 - 955
  • [8] Methods and Strategies to Quantify Phase Separation of Disordered Proteins
    Ceballos, Alfredo Vidal
    McDonald, Charles J.
    Elbaum-Garfinkle, Shana
    INTRINSICALLY DISORDERED PROTEINS, 2018, 611 : 31 - 50
  • [9] Inducing phase separation using artificial disordered proteins
    Arunima Singh
    Nature Methods, 2020, 17 : 955 - 955
  • [10] Predicting disordered regions in proteins using the profiles of amino acid indices
    Han, Pengfei
    Zhang, Xiuzhen
    Feng, Zhi-Ping
    BMC BIOINFORMATICS, 2009, 10