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

Esteban Meca, Anatol W. Fritsch, Juan Iglesias--Artola, Simone Reber, Barbara Wagner, Technische Informationsbibliothek (TIB)
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
more » ... 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.
doi:10.34657/8631 fatcat:m34awwikkzck7bsaf5sd6yr334