TY - JOUR
T1 - Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles
AU - Wei, Ming Tzo
AU - Elbaum-Garfinkle, Shana
AU - Holehouse, Alex S.
AU - Chen, Carlos Chih Hsiung
AU - Feric, Marina
AU - Arnold, Craig B.
AU - Priestley, Rodney D.
AU - Pappu, Rohit V.
AU - Brangwynne, Clifford Paul
N1 - Publisher Copyright:
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2017
Y1 - 2017
N2 - 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, lowdensity (semi-dilute) liquids, whose structural features are likely to strongly impact biological function.
AB - 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, lowdensity (semi-dilute) liquids, whose structural features are likely to strongly impact biological function.
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U2 - 10.1038/NCHEM.2803
DO - 10.1038/NCHEM.2803
M3 - Article
C2 - 29064502
AN - SCOPUS:85030031088
SN - 1755-4330
VL - 9
JO - Nature chemistry
JF - Nature chemistry
IS - 11
M1 - 2803
ER -