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Clathrin-mediated endocytosis involves cargo selection and membrane budding into vesicles with the aid of a protein coat. Formation of invaginated pits on the plasma membrane and subsequent budding of vesicles is an energetically demanding process that involves the cooperation of clathrin with many different proteins. Here we investigate the role of the brain-enriched protein epsin 1 in this process. Epsin is targeted to areas of endocytosis by binding the membrane lipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)). We show here that epsin 1 directly modifies membrane curvature on binding to PtdIns(4,5)P(2) in conjunction with clathrin polymerization. We have discovered that formation of an amphipathic alpha-helix in epsin is coupled to PtdIns(4,5)P(2) binding. Mutation of residues on the hydrophobic region of this helix abolishes the ability to curve membranes. We propose that this helix is inserted into one leaflet of the lipid bilayer, inducing curvature. On lipid monolayers epsin alone is sufficient to facilitate the formation of clathrin-coated invaginations.

Original publication

DOI

10.1038/nature01020

Type

Journal article

Journal

Nature

Publication Date

26/09/2002

Volume

419

Pages

361 - 366

Keywords

Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Animals, Biopolymers, Brain, Carrier Proteins, Clathrin, Coated Pits, Cell-Membrane, Crystallography, X-Ray, Drosophila melanogaster, Endocytosis, Humans, Inositol 1,4,5-Trisphosphate, Liposomes, Membrane Proteins, Microscopy, Electron, Models, Molecular, Molecular Sequence Data, Mutation, Neuropeptides, Phosphatidylinositol 4,5-Diphosphate, Protein Binding, Protein Structure, Tertiary, Rats, Vesicular Transport Proteins