+Open data
-Basic information
Entry | Database: PDB / ID: 6u7m | |||||||||
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Title | Cryo-EM Structure of Helical Lipoprotein Lipase | |||||||||
Components | Lipoprotein lipase | |||||||||
Keywords | PROTEIN FIBRIL / HYDROLASE / helical symmetry / lipoprotein lipase | |||||||||
Function / homology | Function and homology information Assembly of active LPL and LIPC lipase complexes / positive regulation of chemokine production => GO:0032722 / lipoprotein lipase / lipoprotein lipase activity / positive regulation of tumor necrosis factor production => GO:0032760 / positive regulation of sequestering of triglyceride / low-density lipoprotein particle mediated signaling / chylomicron remodeling / positive regulation of cholesterol storage / phospholipase A1 ...Assembly of active LPL and LIPC lipase complexes / positive regulation of chemokine production => GO:0032722 / lipoprotein lipase / lipoprotein lipase activity / positive regulation of tumor necrosis factor production => GO:0032760 / positive regulation of sequestering of triglyceride / low-density lipoprotein particle mediated signaling / chylomicron remodeling / positive regulation of cholesterol storage / phospholipase A1 / phosphatidylserine 1-acylhydrolase activity / 1-acyl-2-lysophosphatidylserine acylhydrolase activity / phospholipase A1 activity / phospholipase activity / triglyceride catabolic process / lipase activity / very-low-density lipoprotein particle remodeling / positive regulation of macrophage derived foam cell differentiation / chylomicron / cellular response to nutrient / very-low-density lipoprotein particle / triglyceride lipase activity / positive regulation of chemokine (C-X-C motif) ligand 2 production / heparan sulfate proteoglycan binding / triglyceride homeostasis / cellular response to fatty acid / triglyceride metabolic process / lipoprotein particle binding / apolipoprotein binding / positive regulation of fat cell differentiation / phospholipid metabolic process / response to glucose / lipid catabolic process / positive regulation of interleukin-1 beta production / cholesterol homeostasis / response to bacterium / fatty acid biosynthetic process / positive regulation of inflammatory response / positive regulation of interleukin-6 production / heparin binding / signaling receptor binding / calcium ion binding / cell surface / protein homodimerization activity / extracellular space / plasma membrane Similarity search - Function | |||||||||
Biological species | Bos taurus (cattle) | |||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Gunn, K.H. / Wang, F. / Egelman, E.H. / Neher, S.B. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Proc Natl Acad Sci U S A / Year: 2020 Title: The structure of helical lipoprotein lipase reveals an unexpected twist in lipase storage. Authors: Kathryn H Gunn / Benjamin S Roberts / Fengbin Wang / Joshua D Strauss / Mario J Borgnia / Edward H Egelman / Saskia B Neher / Abstract: Lipases are enzymes necessary for the proper distribution and utilization of lipids in the human body. Lipoprotein lipase (LPL) is active in capillaries, where it plays a crucial role in preventing ...Lipases are enzymes necessary for the proper distribution and utilization of lipids in the human body. Lipoprotein lipase (LPL) is active in capillaries, where it plays a crucial role in preventing dyslipidemia by hydrolyzing triglycerides from packaged lipoproteins. Thirty years ago, the existence of a condensed and inactive LPL oligomer was proposed. Although recent work has shed light on the structure of the LPL monomer, the inactive oligomer remained opaque. Here we present a cryo-EM reconstruction of a helical LPL oligomer at 3.8-Å resolution. Helix formation is concentration-dependent, and helices are composed of inactive dihedral LPL dimers. Heparin binding stabilizes LPL helices, and the presence of substrate triggers helix disassembly. Superresolution fluorescent microscopy of endogenous LPL revealed that LPL adopts a filament-like distribution in vesicles. Mutation of one of the helical LPL interaction interfaces causes loss of the filament-like distribution. Taken together, this suggests that LPL is condensed into its inactive helical form for storage in intracellular vesicles. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6u7m.cif.gz | 2 MB | Display | PDBx/mmCIF format |
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PDB format | pdb6u7m.ent.gz | 1.8 MB | Display | PDB format |
PDBx/mmJSON format | 6u7m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u7/6u7m ftp://data.pdbj.org/pub/pdb/validation_reports/u7/6u7m | HTTPS FTP |
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-Related structure data
Related structure data | 20673MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Symmetry | Helical symmetry: (Circular symmetry: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 30 / Rise per n subunits: 10.88 Å / Rotation per n subunits: 130.05 °) |
Details | Helical parameters can be applied to chains A and a to generate the full helical assembly. |
-Components
#1: Protein | Mass: 53448.789 Da / Num. of mol.: 30 / Source method: isolated from a natural source / Source: (natural) Bos taurus (cattle) / References: UniProt: P11151, lipoprotein lipase |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: filament of lipoprotein lipase / Type: COMPLEX / Entity ID: all / Source: NATURAL | |||||||||||||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: Bos taurus (cattle) | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.35 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Details: 15 mA current | |||||||||||||||||||||||||
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 98 % / Chamber temperature: 295 K / Details: Blot 3 seconds before plunging |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TALOS ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 45000 X / Cs: 2.7 mm / C2 aperture diameter: 70 µm |
Specimen holder | Cryogen: NITROGEN |
Image recording | Average exposure time: 12.8 sec. / Electron dose: 46.6 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of real images: 1764 |
Image scans | Movie frames/image: 32 |
-Processing
Software | Name: PHENIX / Version: dev_2919: / Classification: refinement | |||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 130.05 ° / Axial rise/subunit: 10.88 Å / Axial symmetry: C1 | |||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 157128 | |||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.8 Å / Resolution method: OTHER / Num. of particles: 108911 / Algorithm: BACK PROJECTION Details: model: map FSC 0.38 cutoff; map: map FSC 0.143 cutoff Num. of class averages: 1 / Symmetry type: HELICAL | |||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | |||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 6E7K Pdb chain-ID: A |