Intrinsically disordered proteins drive membrane curvature

David J. Busch, Justin R. Houser, Carl C. Hayden, Michael Sherman, Eileen M. Lafer, Jeanne C. Stachowiak

Research output: Contribution to journalArticle

66 Citations (Scopus)

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.

Original languageEnglish (US)
Article number8875
JournalNature Communications
Volume6
DOIs
StatePublished - Jul 24 2015

Fingerprint

Intrinsically Disordered Proteins
curvature
membranes
proteins
Membranes
Membrane structures
membrane structures
Pressure
Clathrin
assembly
Physiology
physiology
cargo
Membrane Proteins
exclusion
Hydrodynamics
helices
wedges
Cells
diffusivity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Busch, D. J., Houser, J. R., Hayden, C. C., Sherman, M., Lafer, E. M., & Stachowiak, J. C. (2015). Intrinsically disordered proteins drive membrane curvature. Nature Communications, 6, [8875]. https://doi.org/10.1038/ncomms8875

Intrinsically disordered proteins drive membrane curvature. / Busch, David J.; Houser, Justin R.; Hayden, Carl C.; Sherman, Michael; Lafer, Eileen M.; Stachowiak, Jeanne C.

In: Nature Communications, Vol. 6, 8875, 24.07.2015.

Research output: Contribution to journalArticle

Busch, DJ, Houser, JR, Hayden, CC, Sherman, M, Lafer, EM & Stachowiak, JC 2015, 'Intrinsically disordered proteins drive membrane curvature', Nature Communications, vol. 6, 8875. https://doi.org/10.1038/ncomms8875
Busch, David J. ; Houser, Justin R. ; Hayden, Carl C. ; Sherman, Michael ; Lafer, Eileen M. ; Stachowiak, Jeanne C. / Intrinsically disordered proteins drive membrane curvature. In: Nature Communications. 2015 ; Vol. 6.
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