Structural highlights
Function
MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.TRIA1_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 (PubMed:23931759). Likewise, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes (in vitro) and probably functions as a PA transporter across the mitochondrion intermembrane space (in vivo) (PubMed:26071602). Mediates cell survival by inhibiting activation of caspase-9 which prevents induction of apoptosis (PubMed:15735003).[1] [2]
Publication Abstract from PubMed
Conserved 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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Park WR, Nakamura Y. p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway. Cancer Res. 2005 Feb 15;65(4):1197-206. PMID:15735003 doi:http://dx.doi.org/65/4/1197
- ↑ Potting C, Tatsuta T, Konig T, Haag M, Wai T, Aaltonen MJ, Langer T. TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid. Cell Metab. 2013 Aug 6;18(2):287-95. doi: 10.1016/j.cmet.2013.07.008. PMID:23931759 doi:http://dx.doi.org/10.1016/j.cmet.2013.07.008
- ↑ Miliara X, Tatsuta T, Berry JL, Rouse SL, Solak K, Chorev DS, Wu D, Robinson CV, Matthews S, Langer T. Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins. Nat Commun. 2019 Mar 8;10(1):1130. doi: 10.1038/s41467-019-09089-x. PMID:30850607 doi:http://dx.doi.org/10.1038/s41467-019-09089-x
