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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-4771 | ||||||||||||||||||
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Title | S. cerevisiae Niemann-Pick type C Related Protein 1 (NCR1) | ||||||||||||||||||
![]() | post-processed map | ||||||||||||||||||
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Function / homology | ![]() Intestinal lipid absorption / LDL clearance / sterol transport / sterol binding / sphingolipid metabolic process / fungal-type vacuole membrane / cholesterol binding / cholesterol homeostasis / endoplasmic reticulum / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 7.2 Å | ||||||||||||||||||
![]() | Rawson S / Kidmose RT / Muench SP / Pedersen BP | ||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins. Authors: Mikael B L Winkler / Rune T Kidmose / Maria Szomek / Katja Thaysen / Shaun Rawson / Stephen P Muench / Daniel Wüstner / Bjørn Panyella Pedersen / ![]() ![]() Abstract: 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. | ||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 38 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.5 KB 17.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8 KB | Display | ![]() |
Images | ![]() | 119.6 KB | ||
Others | ![]() ![]() ![]() ![]() | 26.5 MB 26.5 MB 31.4 MB 31.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 381.7 KB | Display | ![]() |
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Full document | ![]() | 380.7 KB | Display | |
Data in XML | ![]() | 13.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | post-processed map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.047 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: local resolution filtered.
File | emd_4771_additional.map | ||||||||||||
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Annotation | local resolution filtered. | ||||||||||||
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Density Histograms |
-Additional map: local resolution filtered.
File | emd_4771_additional_1.map | ||||||||||||
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Annotation | local resolution filtered. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 1
File | emd_4771_half_map_1.map | ||||||||||||
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Annotation | Half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map 2
File | emd_4771_half_map_2.map | ||||||||||||
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Annotation | Half map 2 | ||||||||||||
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Density Histograms |
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Sample components
-Entire : NCR1
Entire | Name: NCR1 |
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Components |
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-Supramolecule #1: NCR1
Supramolecule | Name: NCR1 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 133 KDa |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Niemann-Pick type C-related protein 1
Macromolecule | Name: Niemann-Pick type C-related protein 1 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MNVLWIIALV GQLMRLVQGT ATCAMYGNCG KKSVFGNELP CPVPRSFEPP VLSDETSKLL VEVCGEEWKE VRYACCTKDQ VVALRDNLQK AQPLISSCPA CLKNFNNLFC HFTCAADQGR FVNITKVEKS KEDKDIVAEL DVFMNSSWAS EFYDSCKNIK FSATNGYAMD ...String: MNVLWIIALV GQLMRLVQGT ATCAMYGNCG KKSVFGNELP CPVPRSFEPP VLSDETSKLL VEVCGEEWKE VRYACCTKDQ VVALRDNLQK AQPLISSCPA CLKNFNNLFC HFTCAADQGR FVNITKVEKS KEDKDIVAEL DVFMNSSWAS EFYDSCKNIK FSATNGYAMD LIGGGAKNYS QFLKFLGDAK PMLGGSPFQI NYKYDLANEE KEWQEFNDEV YACDDAQYKC ACSDCQESCP HLKPLKDGVC KVGPLPCFSL SVLIFYTICA LFAFMWYYLC KRKKNGAMIV DDDIVPESGS LDESETNVFE SFNNETNFFN GKLANLFTKV GQFSVENPYK ILITTVFSIF VFSFIIFQYA TLETDPINLW VSKNSEKFKE KEYFDDNFGP FYRTEQIFVV NETGPVLSYE TLHWWFDVEN FITEELQSSE NIGYQDLCFR PTEDSTCVIE SFTQYFQGAL PNKDSWKREL QECGKFPVNC LPTFQQPLKT NLLFSDDDIL NAHAFVVTLL LTNHTQSANR WEERLEEYLL DLKVPEGLRI SFNTEISLEK ELNNNNDIST VAISYLMMFL YATWALRRKD GKTRLLLGIS GLLIVLASIV CAAGFLTLFG LKSTLIIAEV IPFLILAIGI DNIFLITHEY DRNCEQKPEY SIDQKIISAI GRMSPSILMS LLCQTGCFLI AAFVTMPAVH NFAIYSTVSV IFNGVLQLTA YVSILSLYEK RSNYKQITGN EETKESFLKT FYFKMLTQKR LIIIIFSAWF FTSLVFLPEI QFGLDQTLAV PQDSYLVDYF KDVYSFLNVG PPVYMVVKNL DLTKRQNQQK ICGKFTTCER DSLANVLEQE RHRSTITEPL ANWLDDYFMF LNPQNDQCCR LKKGTDEVCP PSFPSRRCET CFQQGSWNYN MSGFPEGKDF MEYLSIWINA PSDPCPLGGR APYSTALVYN ETSVSASVFR TAHHPLRSQK DFIQAYSDGV RISSSFPELD MFAYSPFYIF FVQYQTLGPL TLKLIGSAII LIFFISSVFL QNIRSSFLLA LVVTMIIVDI GALMALLGIS LNAVSLVNLI ICVGLGVEFC VHIVRSFTVV PSETKKDANS RVLYSLNTIG ESVIKGITLT KFIGVCVLAF AQSKIFDVFY FRMWFTLIIV AALHALLFLP ALLSLFGGES YRDDSIEAED LVPRGSGGGG SGGGGSGGHH HHHHHHHH |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 6.5 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 2.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |