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-Structure paper
タイトル | Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins. |
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ジャーナル・号・ページ | Cell, Vol. 179, Issue 2, Page 485-497.e18, Year 2019 |
掲載日 | 2019年10月3日 |
![]() | Mikael B L Winkler / Rune T Kidmose / Maria Szomek / Katja Thaysen / Shaun Rawson / Stephen P Muench / Daniel Wüstner / Bjørn Panyella Pedersen / ![]() ![]() |
PubMed 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. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 2.8 - 7.2 Å |
構造データ | ![]() EMDB-4771: ![]() PDB-6r4l: ![]() PDB-6r4m: ![]() PDB-6r4n: |
化合物 | ![]() ChemComp-ERG: ![]() ChemComp-NAG: ![]() ChemComp-SO4: |
由来 |
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![]() | LIPID TRANSPORT / Vacuole / Ergosterol / membrane protein |