Structural insight into the TRIAP1/PRELI-like domain family of mitochondrial phospholipid transfer complexes

EMBO Rep. 2015 Jul;16(7):824-35. doi: 10.15252/embr.201540229. Epub 2015 Jun 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Biological Transport
  • Crystallography, X-Ray
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Proteins / metabolism
  • Molecular Chaperones / metabolism
  • Molecular Sequence Data
  • Phospholipids / chemistry
  • Phospholipids / metabolism*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Alignment


  • APBB1IP protein, human
  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones
  • Phospholipids
  • TRIAP1 protein, human

Associated data

  • PDB/4XZS
  • PDB/4XZV