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Predicting Disordered Regions Driving Phase Separation of Proteins Under Variable Salt Concentration

Esteban MecaAnatol W. FritschJuan Manuel Iglesias ArtolaSimone ReberBarbara Wagner

出版	Berlin : Weierstraß-Institut für Angewandte Analysis und Stochastik, 2021
URL	http://books.google.com.hk/books?id=MeHxzgEACAAJ&hl=&source=gbs_api

註釋

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 approximation (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 promotes 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.