Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles.

TitlePhase behaviour of disordered proteins underlying low density and high permeability of liquid organelles.
Publication TypeJournal Article
Year of Publication2017
AuthorsWei, M-T, Elbaum-Garfinkle, S, Holehouse, AS, Chen, CChih-Hsiun, Feric, M, Arnold, CB, Priestley, RD, Pappu, RV, Brangwynne, CP
JournalNat Chem
Volume9
Issue11
Pagination1118-1125
Date Published2017 Nov
ISSN1755-4349
Abstract

Many intracellular membraneless organelles form via phase separation of intrinsically disordered proteins (IDPs) or regions (IDRs). These include the Caenorhabditis elegans protein LAF-1, which forms P granule-like droplets in vitro. However, the role of protein disorder in phase separation and the macromolecular organization within droplets remain elusive. Here, we utilize a novel technique, ultrafast-scanning fluorescence correlation spectroscopy, to measure the molecular interactions and full coexistence curves (binodals), which quantify the protein concentration within LAF-1 droplets. The binodals of LAF-1 and its IDR display a number of unusual features, including 'high concentration' binodal arms that correspond to remarkably dilute droplets. We find that LAF-1 and other in vitro and intracellular droplets are characterized by an effective mesh size of ∼3-8 nm, which determines the size scale at which droplet properties impact molecular diffusion and permeability. These findings reveal how specific IDPs can phase separate to form permeable, low-density (semi-dilute) liquids, whose structural features are likely to strongly impact biological function.

DOI10.1038/nchem.2803
Alternate JournalNat Chem
PubMed ID29064502