@article{ba38a1609e3844f69fde6ac943949de4,
title = "Intrinsically disordered proteins drive membrane curvature",
abstract = "Assembly of highly curved membrane structures is essential to cellular physiology. The prevailing view has been that proteins with curvature-promoting structural motifs, such as wedge-like amphipathic helices and crescent-shaped BAR domains, are required for bending membranes. Here we report that intrinsically disordered domains of the endocytic adaptor proteins, Epsin1 and AP180 are highly potent drivers of membrane curvature. This result is unexpected since intrinsically disordered domains lack a well-defined three-dimensional structure. However, in vitro measurements of membrane curvature and protein diffusivity demonstrate that the large hydrodynamic radii of these domains generate steric pressure that drives membrane bending. When disordered adaptor domains are expressed as transmembrane cargo in mammalian cells, they are excluded from clathrin-coated pits. We propose that a balance of steric pressure on the two surfaces of the membrane drives this exclusion. These results provide quantitative evidence for the influence of steric pressure on the content and assembly of curved cellular membrane structures.",
author = "Busch, {David J.} and Houser, {Justin R.} and Hayden, {Carl C.} and Sherman, {Michael B.} and Lafer, {Eileen M.} and Stachowiak, {Jeanne C.}",
note = "Funding Information: J.C.S. acknowledges support from the National Institutes of Health (1R01GM112065 to Stachowiak in support of Busch, Houser, and Hayden) as well as startup funding from The University of Texas at Austin. E.M.L. acknowledges support from the National Institutes of Health (NIH-NS029051 to Lafer). We thank Dr Ernst Ungewickell (Hannover Medical School) for providing the Epsin1 CTD and AP180 CTD plasmids, Dr Thomas Kirchhausen (Harvard Medical School) for providing a transferrin receptor plasmid and Dr Anthony Brown (Ohio State University) for making the neurofilament-M plasmid available through Addgene. We thank Dr Dwight Romanovicz and the ICMB Microscopy Facility at UT Austin for assistance with electron microscopy. We thank Dr Allen Liu (University of Michigan) and Dr Sandra Schmid (UT Southwestern Medical School) for providing the RPE cell line stably expressing mCherry-labelled CLC used in this study, as well as for helpful advice using the clathrin pit detection software, freely provided by the lab of Dr Gaudenz Danuser (Harvard Medical School). We thank Dr Terry O{\textquoteright}Halloran (UT Austin) for feedback on this project, as well as undergraduate researchers Jerin Jose, Saad Jafri and Brian Li for assistance with preliminary experiments. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = jul,
day = "24",
doi = "10.1038/ncomms8875",
language = "English (US)",
volume = "6",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}