6r4l
From Proteopedia
Crystal structure of S. cerevisia Niemann-Pick type C protein NCR1
Structural highlights
Function[NPC1_YEAST] Involved in sphingolipid trafficking. May recycle sphingolipids between cellular membranous compartments.[1] [2] Publication Abstract from PubMedNiemann-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 A 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. Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins.,Winkler MBL, Kidmose RT, Szomek M, Thaysen K, Rawson S, Muench SP, Wustner D, Pedersen BP Cell. 2019 Oct 3;179(2):485-497.e18. doi: 10.1016/j.cell.2019.08.038. Epub 2019, Sep 19. PMID:31543266[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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