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Molecular basis of the potent membrane-remodeling activity of the epsin 1 N-terminal homology domain

  • Author(s): Yoon, Y
  • Tong, J
  • Lee, PJ
  • Albanese, A
  • Bhardwaj, N
  • Källberg, M
  • Digman, MA
  • Lu, H
  • Gratton, E
  • Shin, YK
  • Cho, W
  • et al.
Abstract

The mechanisms by which cytosolic proteins reversibly bind the membrane and induce the curvature for membrane trafficking and remodeling remain elusive. The epsin N-terminal homology (ENTH) domain has potent vesicle tubulation activity despite a lack of intrinsic molecular curvature. EPR revealed that the N-terminal α-helix penetrates the phosphatidylinositol 4,5-bisphosphate-containing membrane at a unique oblique angle and concomitantly interacts closely with helices from neighboring molecules in an antiparallel orientation. The quantitative fluorescence microscopy showed that the formation of highly ordered ENTH domain complexes beyond a critical size is essential for its vesicle tubulation activity. The mutations that interfere with the formation of large ENTH domain complexes abrogated the vesicle tubulation activity. Furthermore, the same mutations in the intact epsin 1 abolished its endocytic activity in mammalian cells. Collectively, these results show that the ENTH domain facilitates the cellular membrane budding and fission by a novel mechanism that is distinct from that proposed for BAR domains. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

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