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

DOI: 10.15252/embr.201540229
PMID: 26071602

Authors: X. Miliara (Imperial College London) , J. Garnett (Imperial College London) , T. Tatsuta (University of Cologne) , F. Abid Ali (Imperial College London) , H. Baldie (Imperial College London) , I. Perez-dorado (Imperial College London) , P. Simpson (Imperial College London) , E. Yague (Imperial College London) , T. Langer (University of Cologne) , S. Matthews (Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Embo Reports , VOL 16 (7) , PAGES 824 - 835

State: Published (Approved)
Published: June 2015
Diamond Proposal Number(s): 9424

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.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography