Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis

Cell. 2007 May 18;129(4):761-72. doi: 10.1016/j.cell.2007.03.040.


Pombe Cdc15 homology (PCH) proteins play an important role in a variety of actin-based processes, including clathrin-mediated endocytosis (CME). The defining feature of the PCH proteins is an evolutionarily conserved EFC/F-BAR domain for membrane association and tubulation. In the present study, we solved the crystal structures of the EFC domains of human FBP17 and CIP4. The structures revealed a gently curved helical-bundle dimer of approximately 220 A in length, which forms filaments through end-to-end interactions in the crystals. The curved EFC dimer fits a tubular membrane with an approximately 600 A diameter. We subsequently proposed a model in which the curved EFC filament drives tubulation. In fact, striation of tubular membranes was observed by phase-contrast cryo-transmission electron microscopy, and mutations that impaired filament formation also impaired membrane tubulation and cell membrane invagination. Furthermore, FBP17 is recruited to clathrin-coated pits in the late stage of CME, indicating its physiological role.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • COS Cells
  • Carrier Proteins / chemistry*
  • Carrier Proteins / ultrastructure
  • Cell Membrane Structures / metabolism*
  • Cell Membrane Structures / ultrastructure
  • Chlorocebus aethiops
  • Clathrin / metabolism
  • Clathrin / ultrastructure
  • Coated Pits, Cell-Membrane / metabolism*
  • Coated Pits, Cell-Membrane / ultrastructure
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Dimerization
  • Endocytosis / physiology*
  • Humans
  • Mice
  • Microtubule-Associated Proteins / chemistry*
  • Microtubule-Associated Proteins / ultrastructure
  • Minor Histocompatibility Antigens
  • Models, Molecular
  • Mutation / physiology
  • NIH 3T3 Cells
  • Protein Structure, Tertiary / physiology


  • Carrier Proteins
  • Clathrin
  • FNBP1 protein, human
  • Microtubule-Associated Proteins
  • Minor Histocompatibility Antigens
  • TRIP10 protein, human