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.
Atsushi Shimada  1 ,  Hideaki Niwa ,  Kazuya Tsujita ,  Shiro Suetsugu ,  Koji Nitta ,  Kyoko Hanawa-Suetsugu ,  Ryogo Akasaka ,  Yuri Nishino ,  Mitsutoshi Toyama ,  Lirong Chen ,  Zhi-Jie Liu ,  Bi-Cheng Wang ,  Masaki Yamamoto ,  Takaho Terada ,  Atsuo Miyazawa ,  Akiko Tanaka ,  Sumio Sugano ,  Mikako Shirouzu ,  Kuniaki Nagayama ,  Tadaomi Takenawa ,  Shigeyuki Yokoyama
Affiliations
  • 1. RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
PMID: 17512409 DOI: 10.1016/j.cell.2007.03.040
Abstract

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.