Author/Authors :
Atsushi Shimada، نويسنده , , Hideaki Niwa، نويسنده , , Kazuya Tsujita، نويسنده , , Shiro Suetsugu، نويسنده , , Koji Nitta، نويسنده , , Kyoko Hanawa-Suetsugu، نويسنده , , Ryogo Akasaka، نويسنده , , Yuri Nishino، نويسنده , , Mitsutoshi Toyama، نويسنده , , Lirong Chen، نويسنده , , Zhi-Jie Liu، نويسنده , , Bi-Cheng Wang، نويسنده , , Masaki Yamamoto، نويسنده , , Takaho Terada، نويسنده , , Atsuo Miyazawa، نويسنده , , Akiko Tanaka، نويسنده , , Sumio Sugano، نويسنده , , Mikako Shirouzu، نويسنده , , Kuniaki Nagayama، نويسنده , , Tadaomi Takenawa، نويسنده , , et al.، نويسنده ,
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 ∼220 Å in length, which forms filaments through end-to-end interactions in the crystals. The curved EFC dimer fits a tubular membrane with an ∼600 Å 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.
