title: Mechanistic insights into the lipid interaction of an ancient saposin-like protein.
abstract: The members of the expanding family of saposin-like proteins (SAPLIPs) have various biological functions in plants, animals, and humans. In addition to a similar protein backbone, these proteins have in common the fact that they interact with lipid membranes. According to their phylogenetic position, it has long been thought that amoeboid protozoans produce archetypes of SAPLIPs and that these are lytic proteins that can perforate membranes of prokaryotic and eukaryotic target cells. Here, we show that an amoebic SAPLIP from Entamoeba invadens does not form lytic pores in membranes but displays several characteristics that are known from human saposins. The protein named invaposin changes the conformation from a closed to an open form in the presence of lipid membranes, acts in a pH-dependent manner, selectively binds anionic lipids, aggregates lipid vesicles of the preferred composition, and dimerizes upon acidification. Our data indicate that the principal features of the lipid-binding saposins evolved long before the appearance of the vertebrate lineage and push the origin of saposins even deeper down the phylogenetic tree to unicellular organisms.
authors.affiliation: Zoological Institute, Comparative Immunobiology, University of Kiel , Olshausenstrasse 40, 24098 Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Michalek
authors.forename: Matthias
authors.initials: M
authors.lastname: Leippe
mesh_terms: D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability; D004747:Entamoeba / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D049231:Saposins / Q000737:chemistry* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D008051:Lipid Bilayers; D008563:Membrane Lipids; D011994:Recombinant Proteins; D049231:Saposins