6i3y
Crystal structure of the human mitochondrial PRELID1K58V-TRIAP1 complex with PS
Structural highlights
FunctionPRLD1_HUMAN Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane. Regulates the mitochondrial apoptotic pathway in primary Th cells. Regulates Th cell differentiation by down-regulating STAT6 thereby reducing IL-4-induced Th2 cell number. May be important for the development of vital and immunocompetent organs.[1] [2] [3] Publication Abstract from PubMedConserved lipid transfer proteins of the Ups/PRELI family regulate lipid accumulation in mitochondria by shuttling phospholipids in a lipid-specific manner across the intermembrane space. Here, we combine structural analysis, unbiased genetic approaches in yeast and molecular dynamics simulations to unravel determinants of lipid specificity within the conserved Ups/PRELI family. We present structures of human PRELID1-TRIAP1 and PRELID3b-TRIAP1 complexes, which exert lipid transfer activity for phosphatidic acid and phosphatidylserine, respectively. Reverse yeast genetic screens identify critical amino acid exchanges that broaden and swap their lipid specificities. We find that amino acids involved in head group recognition and the hydrophobicity of flexible loops regulate lipid entry into the binding cavity. Molecular dynamics simulations reveal different membrane orientations of PRELID1 and PRELID3b during the stepwise release of lipids. Our experiments thus define the structural determinants of lipid specificity and the dynamics of lipid interactions by Ups/PRELI proteins. Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins.,Miliara X, Tatsuta T, Berry JL, Rouse SL, Solak K, Chorev DS, Wu D, Robinson CV, Matthews S, Langer T Nat Commun. 2019 Mar 8;10(1):1130. doi: 10.1038/s41467-019-09089-x. PMID:30850607[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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