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
Date Published2017 Nov
KeywordsIntrinsically Disordered Proteins, Molecular Dynamics Simulation, Monte Carlo Method, Organelles, Particle Size, Permeability, Spectrometry, Fluorescence

<p>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.</p>

Alternate JournalNat Chem
PubMed ID29064502
PubMed Central IDPMC9719604
Grant ListDP2 GM105437 / GM / NIGMS NIH HHS / United States
K99 NS096217 / NS / NINDS NIH HHS / United States
R01 NS056114 / NS / NINDS NIH HHS / United States