title: Homology of SMP domains to the TULIP superfamily of lipid-binding proteins provides a structural basis for lipid exchange between ER and mitochondria.
abstract: Mitochondria must uptake some phospholipids from the endoplasmic reticulum (ER) for the biogenesis of their membranes. They convert one of these lipids, phosphatidylserine, to phosphatidylethanolamine, which can be re-exported via the ER to all other cellular membranes. The mechanisms underlying these exchanges between ER and mitochondria are poorly understood. Recently, a complex termed ER-mitochondria encounter structure (ERMES) was shown to be necessary for phospholipid exchange in budding yeast. However, it is unclear whether this complex is merely an inter-organelle tether or also the transporter. ERMES consists of four proteins: Mdm10, Mdm34 (Mmm2), Mdm12 and Mmm1, three of which contain the uncharacterized SMP domain common to a number of eukaryotic membrane-associated proteins. Here, we show that the SMP domain belongs to the TULIP superfamily of lipid/hydrophobic ligand-binding domains comprising members of known structure. This relationship suggests that the SMP domains of the ERMES complex mediate lipid exchange between ER and mitochondria.
authors.affiliation: Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Klaus O
authors.initials: KO
authors.lastname: Kopec
authors.forename: Vikram
authors.initials: V
authors.lastname: Alva
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Lupas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010743:Phospholipids