6I3V

x-ray structure of the human mitochondrial PRELID1 in complex with TRIAP1

6I3V の概要

• エントリーDOI: 10.2210/pdb6i3v/pdb
• 分子名称: PRELI domain-containing protein 1, mitochondrial, TP53-regulated inhibitor of apoptosis 1, MYRISTIC ACID, ... (6 entities in total)
• 機能のキーワード: prelid1 lipid transport mitochondrial protein, lipid binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 59855.20

構造登録者

Berry, J.L.,Miliara, X.,Morgan, R.M.L.,Matthews, S.J. (登録日: 2018-11-07, 公開日: 2019-03-20, 最終更新日: 2024-11-20)

主引用文献

Miliara, X.,Tatsuta, T.,Berry, J.L.,Rouse, S.L.,Solak, K.,Chorev, D.S.,Wu, D.,Robinson, C.V.,Matthews, S.,Langer, T.
Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins.
Nat Commun, 10:1130-1130, 2019

PubMed Abstract: 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.

PubMed: 30850607
DOI: 10.1038/s41467-019-09089-x

実験手法

X-RAY DIFFRACTION (1.98 Å)