6CBC

Crystal structure of an N-terminal fragment of Vps13.

6CBC の概要

• エントリーDOI: 10.2210/pdb6cbc/pdb
• 分子名称: Vacuolar protein sorting-associated protein (1 entity in total)
• 機能のキーワード: lipid transfer protein, membrane trafficking, endoplasmic reticulum, mitochondria, endosomes, lipid binding protein
• 由来する生物種: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78468.95

構造登録者

Kumar, N.,Horenkamp, F.A.,Reinisch, K.M. (登録日: 2018-02-02, 公開日: 2018-08-08, 最終更新日: 2024-10-09)

主引用文献

Kumar, N.,Leonzino, M.,Hancock-Cerutti, W.,Horenkamp, F.A.,Li, P.,Lees, J.A.,Wheeler, H.,Reinisch, K.M.,De Camilli, P.
VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites.
J. Cell Biol., 217:3625-3639, 2018

PubMed Abstract: Mutations in the human VPS13 genes are responsible for neurodevelopmental and neurodegenerative disorders including chorea acanthocytosis (VPS13A) and Parkinson's disease (VPS13C). The mechanisms of these diseases are unknown. Genetic studies in yeast hinted that Vps13 may have a role in lipid exchange between organelles. In this study, we show that the N-terminal portion of VPS13 is tubular, with a hydrophobic cavity that can solubilize and transport glycerolipids between membranes. We also show that human VPS13A and VPS13C bind to the ER, tethering it to mitochondria (VPS13A), to late endosome/lysosomes (VPS13C), and to lipid droplets (both VPS13A and VPS13C). These findings identify VPS13 as a lipid transporter between the ER and other organelles, implicating defects in membrane lipid homeostasis in neurological disorders resulting from their mutations. Sequence and secondary structure similarity between the N-terminal portions of Vps13 and other proteins such as the autophagy protein ATG2 suggest lipid transport roles for these proteins as well.

PubMed: 30093493
DOI: 10.1083/jcb.201807019

実験手法

X-RAY DIFFRACTION (3 Å)