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Free keywords:
Adaptor Proteins, Signal Transducing/*chemistry/*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/*metabolism
Membrane Proteins/*chemistry/*metabolism
Mitochondria/*metabolism
Mitochondrial Membranes/*metabolism
Mitochondrial Proteins/metabolism
Molecular Chaperones/metabolism
Molecular Sequence Data
Phospholipids/chemistry/*metabolism
Protein Structure, Secondary
Protein Structure, Tertiary
Sequence Alignment
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.
