Title | Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Wei, M-T, Elbaum-Garfinkle, S, Holehouse, AS, Chen, CChih-Hsiun, Feric, M, Arnold, CB, Priestley, RD, Pappu, RV, Brangwynne, CP |
Journal | Nat Chem |
Volume | 9 |
Issue | 11 |
Pagination | 1118-1125 |
Date Published | 2017 Nov |
ISSN | 1755-4349 |
Keywords | Intrinsically Disordered Proteins, Molecular Dynamics Simulation, Monte Carlo Method, Organelles, Particle Size, Permeability, Spectrometry, Fluorescence |
Abstract | <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> |
DOI | 10.1038/nchem.2803 |
Alternate Journal | Nat Chem |
PubMed ID | 29064502 |
PubMed Central ID | PMC9719604 |
Grant List | DP2 GM105437 / GM / NIGMS NIH HHS / United States K99 NS096217 / NS / NINDS NIH HHS / United States R01 NS056114 / NS / NINDS NIH HHS / United States |