Amphiphysin BAR domain
Drosophila melanogaster (fruit fly)
Amphiphysins are localized around cell-membranes. They cooperate with various proteins in order to promote the deformation of a cell-membrane and the formation of a tube during endocytosis through which a substance is taken from the outside of the cell into the inside, forming a vesicle of a cell-membrane. The BAR (Bin/amphiphysin/Rvs) domain found in amphiphysins is conserved in various proteins associated with the formation of vesicles. Vesicle formation requires a curved membrane and the BAR domain senses curvature on the membrane to induces it to form a vesicle. In Drosophila, amphiphysin is associated with the muscle T-tubule network and with membrane deformation. It has also been shown that the mammalian amphiphysin2 is essential for the generation of muscle T-tubes because it directs the deforming and tabulating of a cell-membrane.
The structure of the BAR domain in Drosophila amphiphysin has been determined. This domain is a homodimer and each monomer is constructed of three long, slightly bent alpha-helices. Around the dimer interface, six helices form a helix-bundle. The dimer is curved due to the intersection of the two monomers and the partially bent helices. The curved BAR domain binds to the curved membrane more tightly than the flat membrane due to the use of its concave surface and interacts preferably with negatively charged membranes. As a result of the formation of the dimer, the BAR domain is primed for vesicle formation. The BAR domain containing the N-terminal amphipathic alpha-helix (N-BAR), which is essential for the formation and stability of the muscle T-tubule network, is more active for the sensing and tabulating of curved membranes than the BAR domain alone. For various proteins related to membrane remodeling and vesicle generation including the BAR domain, the analysis of this structure has provided new insights.
Protein Data Bank (PDB)
Peter, B.J. Kent, H.M. Mills, I.G. Vallis, Y. Butler, J.G. Evans, P.R. Mcmahon, H.T.; "Bar Domains as Sensors of Membrane Curvature: The Amphiphysin Bar Structure"; Science; (2004) 303:495-499.PubMed:14645856
author: Yuko Tsuchiya