title: Structural insight into the TRIAP1/PRELI-like domain family of mitochondrial phospholipid transfer complexes.
abstract: The composition of the mitochondrial membrane is important for its architecture and proper function. Mitochondria depend on a tightly regulated supply of phospholipid via intra-mitochondrial synthesis and by direct import from the endoplasmic reticulum. The Ups1/PRELI-like family together with its mitochondrial chaperones (TRIAP1/Mdm35) represent a unique heterodimeric lipid transfer system that is evolutionary conserved from yeast to man. Work presented here provides new atomic resolution insight into the function of a human member of this system. Crystal structures of free TRIAP1 and the TRIAP1-SLMO1 complex reveal how the PRELI domain is chaperoned during import into the intermembrane mitochondrial space. The structural resemblance of PRELI-like domain of SLMO1 with that of mammalian phoshatidylinositol transfer proteins (PITPs) suggest that they share similar lipid transfer mechanisms, in which access to a buried phospholipid-binding cavity is regulated by conformationally adaptable loops.
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Xeni
authors.initials: X
authors.lastname: Miliara
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK School of Biological and Chemical Sciences, Joseph Priestley Building Queen Mary University of London, London, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Garnett
authors.affiliation: Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tatsuta
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Ferdos
authors.initials: F
authors.lastname: Abid Ali
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Heather
authors.initials: H
authors.lastname: Baldie
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Pérez-Dorado
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Simpson
authors.affiliation: Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Yague
authors.affiliation: Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Langer
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK s.j.matthews@imperial.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Matthews
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D001692:Biological Transport; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: C493340:APBB1IP protein, human; D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D010743:Phospholipids; C498536:TRIAP1 protein, human