- PDB-6r4n: Crystal structure of S. cerevisia Niemann-Pick type C protein NPC... -
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基本情報
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データベース: PDB / ID: 6r4n
タイトル
Crystal structure of S. cerevisia Niemann-Pick type C protein NPC2 with ergosterol bound
要素
Phosphatidylglycerol/phosphatidylinositol transfer protein
キーワード
LIPID TRANSPORT / Vacuole (液胞) / Ergosterol (エルゴステロール)
機能・相同性
機能・相同性情報
fungal-type vacuole lumen / intracellular sterol transport / sterol transport / sterol binding / fungal-type vacuole 類似検索 - 分子機能
ML domain, phosphatidylinositol/phosphatidylglycerol transfer protein / GM2-AP, lipid-recognition domain superfamily / Sterol transport protein NPC2-like / ML domain / MD-2-related lipid-recognition domain / Domain involved in innate immunity and lipid metabolism. / Immunoglobulin E-set 類似検索 - ドメイン・相同性
エルゴステロール / Phosphatidylglycerol/phosphatidylinositol transfer protein 類似検索 - 構成要素
ジャーナル: Cell / 年: 2019 タイトル: Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins. 著者: Mikael B L Winkler / Rune T Kidmose / Maria Szomek / Katja Thaysen / Shaun Rawson / Stephen P Muench / Daniel Wüstner / Bjørn Panyella Pedersen / 要旨: Niemann-Pick type C (NPC) proteins are essential for sterol homeostasis, believed to drive sterol integration into the lysosomal membrane before redistribution to other cellular membranes. Here, ...Niemann-Pick type C (NPC) proteins are essential for sterol homeostasis, believed to drive sterol integration into the lysosomal membrane before redistribution to other cellular membranes. Here, using a combination of crystallography, cryo-electron microscopy, and biochemical and in vivo studies on the Saccharomyces cerevisiae NPC system (NCR1 and NPC2), we present a framework for sterol membrane integration. Sterols are transferred between hydrophobic pockets of vacuolar NPC2 and membrane-protein NCR1. NCR1 has its N-terminal domain (NTD) positioned to deliver a sterol to a tunnel connecting NTD to the luminal membrane leaflet 50 Å away. A sterol is caught inside this tunnel during transport, and a proton-relay network of charged residues in the transmembrane region is linked to this tunnel supporting a proton-driven transport mechanism. We propose a model for sterol integration that clarifies the role of NPC proteins in this essential eukaryotic pathway and that rationalizes mutations in patients with Niemann-Pick disease type C.
A: Phosphatidylglycerol/phosphatidylinositol transfer protein B: Phosphatidylglycerol/phosphatidylinositol transfer protein C: Phosphatidylglycerol/phosphatidylinositol transfer protein D: Phosphatidylglycerol/phosphatidylinositol transfer protein E: Phosphatidylglycerol/phosphatidylinositol transfer protein F: Phosphatidylglycerol/phosphatidylinositol transfer protein G: Phosphatidylglycerol/phosphatidylinositol transfer protein H: Phosphatidylglycerol/phosphatidylinositol transfer protein I: Phosphatidylglycerol/phosphatidylinositol transfer protein ヘテロ分子