Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis.
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.
Shimada
Atsushi
A
RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
Niwa
Hideaki
H
Tsujita
Kazuya
K
Suetsugu
Shiro
S
Nitta
Koji
K
Hanawa-Suetsugu
Kyoko
K
Akasaka
Ryogo
R
Nishino
Yuri
Y
Toyama
Mitsutoshi
M
Chen
Lirong
L
Liu
Zhi-Jie
ZJ
Wang
Bi-Cheng
BC
Yamamoto
Masaki
M
Terada
Takaho
T
Miyazawa
Atsuo
A
Tanaka
Akiko
A
Sugano
Sumio
S
Shirouzu
Mikako
M
Nagayama
Kuniaki
K
Takenawa
Tadaomi
T
Yokoyama
Shigeyuki
S
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000648:ultrastructure; D021961:Cell Membrane Structures / Q000378:metabolism* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000378:metabolism / Q000648:ultrastructure; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism* / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D019281:Dimerization; D004705:Endocytosis / Q000502:physiology*; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000648:ultrastructure; D015778:Minor Histocompatibility Antigens; D008958:Models, Molecular; D009154:Mutation / Q000502:physiology; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary / Q000502:physiology
D002352:Carrier Proteins; D002966:Clathrin; C433770:FNBP1 protein, human; D050556:Fatty Acid-Binding Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C406285:TRIP10 protein, human