Intrinsically disordered proteins drive membrane curvature

Nat Commun. 2015 Jul 24;6:7875. doi: 10.1038/ncomms8875.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Cell Membrane / physiology*
  • Cell Shape
  • Cells, Cultured
  • Clathrin-Coated Vesicles / physiology*
  • Humans
  • Intrinsically Disordered Proteins / physiology*
  • Monomeric Clathrin Assembly Proteins / metabolism*
  • Protein Structure, Tertiary

Substances

  • Adaptor Proteins, Vesicular Transport
  • Intrinsically Disordered Proteins
  • Monomeric Clathrin Assembly Proteins
  • clathrin assembly protein AP180
  • epsin