+Open data
-Basic information
Entry | Database: PDB / ID: 8erl | |||||||||
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Title | CryoEM Structure of Lipoprotein Lipase Dimer | |||||||||
Components | Lipoprotein lipase | |||||||||
Keywords | HYDROLASE / Dimer / 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 / triglyceride catabolic process / phospholipase activity / lipase activity / very-low-density lipoprotein particle remodeling / positive regulation of macrophage derived foam cell differentiation / cellular response to nutrient / chylomicron / very-low-density lipoprotein particle / triacylglycerol lipase activity / heparan sulfate proteoglycan binding / positive regulation of chemokine (C-X-C motif) ligand 2 production / triglyceride homeostasis / cellular response to fatty acid / triglyceride metabolic process / positive regulation of fat cell differentiation / lipoprotein particle binding / apolipoprotein binding / 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 / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Gunn, K.H. / Neher, S.B. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structure of dimeric lipoprotein lipase reveals a pore adjacent to the active site. Authors: Kathryn H Gunn / Saskia B Neher / Abstract: Lipoprotein lipase (LPL) hydrolyzes triglycerides from circulating lipoproteins, releasing free fatty acids. Active LPL is needed to prevent hypertriglyceridemia, which is a risk factor for ...Lipoprotein lipase (LPL) hydrolyzes triglycerides from circulating lipoproteins, releasing free fatty acids. Active LPL is needed to prevent hypertriglyceridemia, which is a risk factor for cardiovascular disease (CVD). Using cryogenic electron microscopy (cryoEM), we determined the structure of an active LPL dimer at 3.9 Å resolution. This structure reveals an open hydrophobic pore adjacent to the active site residues. Using modeling, we demonstrate that this pore can accommodate an acyl chain from a triglyceride. Known LPL mutations that lead to hypertriglyceridemia localize to the end of the pore and cause defective substrate hydrolysis. The pore may provide additional substrate specificity and/or allow unidirectional acyl chain release from LPL. This structure also revises previous models on how LPL dimerizes, revealing a C-terminal to C-terminal interface. We hypothesize that this active C-terminal to C-terminal conformation is adopted by LPL when associated with lipoproteins in capillaries. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8erl.cif.gz | 150.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8erl.ent.gz | 122.1 KB | Display | PDB format |
PDBx/mmJSON format | 8erl.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8erl_validation.pdf.gz | 841.3 KB | Display | wwPDB validaton report |
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Full document | 8erl_full_validation.pdf.gz | 848.3 KB | Display | |
Data in XML | 8erl_validation.xml.gz | 39.9 KB | Display | |
Data in CIF | 8erl_validation.cif.gz | 58.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/er/8erl ftp://data.pdbj.org/pub/pdb/validation_reports/er/8erl | HTTPS FTP |
-Related structure data
Related structure data | 28554MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 53448.789 Da / Num. of mol.: 2 / 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: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Lipoprotein Lipase Dimer / Type: COMPLEX / Entity ID: all / Source: NATURAL |
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Molecular weight | Value: 0.101 MDa / Experimental value: NO |
Source (natural) | Organism: Bos taurus (cattle) |
Buffer solution | pH: 8 |
Specimen | Conc.: 0.55 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil |
Vitrification | Cryogen name: ETHANE-PROPANE |
-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 FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 55.1 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 527205 / Symmetry type: POINT | ||||||||||||||||||||||||
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