WIAS Preprint No. 2875, (2021)

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


Authors

  • Meca, Esteban
  • Fritsch, Anatol W.
  • Iglesias--Artola, Juan
  • Reber, Simone
  • Wagner, Barbara
    ORCID: 0000-0001-8306-3645

2020 Mathematics Subject Classification

  • 82B26 65H10

2010 Physics and Astronomy Classification Scheme

  • 87.15.km 87.15.kr 87.15.Zg

Keywords

  • Liquid-liquid phase separation, random phase approximation, intrinsically disordered proteins, phase-separation assays

DOI

10.20347/WIAS.PREPRINT.2875

Abstract

We determine the intrinsically disordered regions (IDRs) of phase separating proteins and investigate their impact on liquid-liquid phase separation (LLPS) with a random-phase approx- imation (RPA) that accounts for variable salt concentration. We focus on two proteins, PGL-3 and FUS, known to undergo LLPS. For PGL-3 we predict that an IDR near the C-terminus pro- motes LLPS, which we validate through direct comparison with in vitro experimental results. For the structurally more complex protein FUS the role of the low complexity (LC) domain in LLPS is not as well understood. Apart from the LC domain we here identify two IDRs, one near the N-terminus and another near the C-terminus. Our RPA analysis of these domains predict that, surprisingly, the IDR at the N-terminus (aa 1-285) and not the LC domain promotes LLPS of FUS by comparison to in vitro experiments under physiological temperature and salt conditions.

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