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Open data
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Basic information
Entry | Database: PDB / ID: 6w5v | |||||||||
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Title | NPC1-NPC2 complex structure at pH 5.5 | |||||||||
![]() | (NPC intracellular cholesterol transporter ...) x 2 | |||||||||
![]() | TRANSPORT PROTEIN / Cholesterol Lysosome | |||||||||
Function / homology | ![]() regulation of isoprenoid metabolic process / glycolipid transport / intracellular sterol transport / cyclodextrin metabolic process / cholesterol storage / membrane raft organization / intracellular cholesterol transport / intracellular lipid transport / intestinal cholesterol absorption / LDL clearance ...regulation of isoprenoid metabolic process / glycolipid transport / intracellular sterol transport / cyclodextrin metabolic process / cholesterol storage / membrane raft organization / intracellular cholesterol transport / intracellular lipid transport / intestinal cholesterol absorption / LDL clearance / negative regulation of epithelial cell apoptotic process / lipid transporter activity / programmed cell death / phospholipid transport / cholesterol transfer activity / bile acid metabolic process / cholesterol transport / establishment of protein localization to membrane / adult walking behavior / cellular response to low-density lipoprotein particle stimulus / lysosomal transport / cholesterol efflux / negative regulation of macroautophagy / cellular response to steroid hormone stimulus / cholesterol binding / protein glycosylation / neurogenesis / response to cadmium ion / negative regulation of TORC1 signaling / cholesterol metabolic process / lysosomal lumen / liver development / cholesterol homeostasis / macroautophagy / response to virus / transmembrane signaling receptor activity / autophagy / endocytosis / nuclear envelope / azurophil granule lumen / virus receptor activity / late endosome membrane / signaling receptor activity / gene expression / lysosome / response to xenobiotic stimulus / symbiont entry into host cell / membrane raft / lysosomal membrane / Neutrophil degranulation / perinuclear region of cytoplasm / enzyme binding / Golgi apparatus / endoplasmic reticulum / extracellular space / extracellular exosome / extracellular region / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4 Å | |||||||||
![]() | Yan, N. / Qian, H.W. / Wu, X.L. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural Basis of Low-pH-Dependent Lysosomal Cholesterol Egress by NPC1 and NPC2. Authors: Hongwu Qian / Xuelan Wu / Ximing Du / Xia Yao / Xin Zhao / Joyce Lee / Hongyuan Yang / Nieng Yan / ![]() ![]() ![]() Abstract: Lysosomal cholesterol egress requires two proteins, NPC1 and NPC2, whose defects are responsible for Niemann-Pick disease type C (NPC). Here, we present systematic structural characterizations that ...Lysosomal cholesterol egress requires two proteins, NPC1 and NPC2, whose defects are responsible for Niemann-Pick disease type C (NPC). Here, we present systematic structural characterizations that reveal the molecular basis for low-pH-dependent cholesterol delivery from NPC2 to the transmembrane (TM) domain of NPC1. At pH 8.0, similar structures of NPC1 were obtained in nanodiscs and in detergent at resolutions of 3.6 Å and 3.0 Å, respectively. A tunnel connecting the N-terminal domain (NTD) and the transmembrane sterol-sensing domain (SSD) was unveiled. At pH 5.5, the NTD exhibits two conformations, suggesting the motion for cholesterol delivery to the tunnel. A putative cholesterol molecule is found at the membrane boundary of the tunnel, and TM2 moves toward formation of a surface pocket on the SSD. Finally, the structure of the NPC1-NPC2 complex at 4.0 Å resolution was obtained at pH 5.5, elucidating the molecular basis for cholesterol handoff from NPC2 to NPC1(NTD). | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 298.1 KB | Display | ![]() |
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PDB format | ![]() | 230.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 60 KB | Display | |
Data in CIF | ![]() | 84.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 21549MC ![]() 6w5rC ![]() 6w5sC ![]() 6w5tC ![]() 6w5uC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-NPC intracellular cholesterol transporter ... , 2 types, 2 molecules AD
#1: Protein | Mass: 146083.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 17932.600 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 3 types, 15 molecules ![](data/chem/img/NAG.gif)
#3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #4: Polysaccharide | beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #5: Sugar | ChemComp-NAG / |
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-Non-polymers , 1 types, 3 molecules ![](data/chem/img/CLR.gif)
#6: Chemical |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: NPC1-NPC2 complex at pH 5.5 / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Value: 0.17 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 101364 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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