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.
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton, Austin, Texas 78712, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Busch
authors.affiliation: Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton, Austin, Texas 78712, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Houser
authors.affiliation: 1] Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton, Austin, Texas 78712, USA [2] Sandia National Laboratories, 7011 East Avenue, Livermore, California 94550, USA.
authors.forename: Carl C
authors.initials: CC
authors.lastname: Hayden
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 1.224 Medical Research Building, Galveston, Texas 77555, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sherman
authors.affiliation: Department of Biochemistry and Center for Biomedical Neuroscience, The University of Texas Health Science Center at San Antonio, UTHSCSA Biochemistry 415B, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Lafer
authors.affiliation: 1] Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton, Austin, Texas 78712, USA [2] Institute for Cellular and Molecular Biology, The University of Texas at Austin, 107 W Dean, Keeton,Texas 78712, USA.
authors.forename: Jeanne C
authors.initials: JC
authors.lastname: Stachowiak
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology*; D048430:Cell Shape; D002478:Cells, Cultured; D022163:Clathrin-Coated Vesicles / Q000502:physiology*; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000502:physiology*; D034041:Monomeric Clathrin Assembly Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D064267:Intrinsically Disordered Proteins; D034041:Monomeric Clathrin Assembly Proteins; C439023:clathrin assembly protein AP180; C114154:epsin