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| | ==Structure of the lipoprotein lipase GPIHBP1 complex that mediates plasma triglyceride hydrolysis== | | ==Structure of the lipoprotein lipase GPIHBP1 complex that mediates plasma triglyceride hydrolysis== |
| - | <StructureSection load='6e7k' size='340' side='right' caption='[[6e7k]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='6e7k' size='340' side='right'caption='[[6e7k]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6e7k]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E7K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E7K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6e7k]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E7K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E7K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LPL, LIPD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GPIHBP1, HBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lipoprotein_lipase Lipoprotein lipase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.34 3.1.1.34] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6e7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e7k OCA], [https://pdbe.org/6e7k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e7k RCSB], [https://www.ebi.ac.uk/pdbsum/6e7k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e7k ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e7k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e7k OCA], [http://pdbe.org/6e7k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e7k RCSB], [http://www.ebi.ac.uk/pdbsum/6e7k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e7k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/LIPL_HUMAN LIPL_HUMAN]] Hyperlipoproteinemia type 5;Familial lipoprotein lipase deficiency. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/HDBP1_HUMAN HDBP1_HUMAN]] Familial chylomicronemia syndrome. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/LIPL_HUMAN LIPL_HUMAN] Hyperlipoproteinemia type 5;Familial lipoprotein lipase deficiency. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LIPL_HUMAN LIPL_HUMAN]] The primary function of this lipase is the hydrolysis of triglycerides of circulating chylomicrons and very low density lipoproteins (VLDL) (PubMed:27578112). Binding to heparin sulfate proteogylcans at the cell surface is vital to the function. The apolipoprotein, APOC2, acts as a coactivator of LPL activity in the presence of lipids on the luminal surface of vascular endothelium (By similarity).<ref>PMID:11342582</ref> <ref>PMID:27578112</ref> [[http://www.uniprot.org/uniprot/HDBP1_HUMAN HDBP1_HUMAN]] Plays a key role in the lipolytic processing of chylomicrons. Required for the transport of lipoprotein lipase LPL into the capillary lumen (By similarity). | + | [https://www.uniprot.org/uniprot/LIPL_HUMAN LIPL_HUMAN] The primary function of this lipase is the hydrolysis of triglycerides of circulating chylomicrons and very low density lipoproteins (VLDL) (PubMed:27578112). Binding to heparin sulfate proteogylcans at the cell surface is vital to the function. The apolipoprotein, APOC2, acts as a coactivator of LPL activity in the presence of lipids on the luminal surface of vascular endothelium (By similarity).<ref>PMID:11342582</ref> <ref>PMID:27578112</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6e7k" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6e7k" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Lipase 3D Structures|Lipase 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lipoprotein lipase]] | + | [[Category: Large Structures]] |
| - | [[Category: Birrane, G]] | + | [[Category: Birrane G]] |
| - | [[Category: Meiyappan, M]] | + | [[Category: Meiyappan M]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-cofactor complex]]
| + | |
| - | [[Category: Lipid degradation]]
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| Structural highlights
Disease
LIPL_HUMAN Hyperlipoproteinemia type 5;Familial lipoprotein lipase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
LIPL_HUMAN The primary function of this lipase is the hydrolysis of triglycerides of circulating chylomicrons and very low density lipoproteins (VLDL) (PubMed:27578112). Binding to heparin sulfate proteogylcans at the cell surface is vital to the function. The apolipoprotein, APOC2, acts as a coactivator of LPL activity in the presence of lipids on the luminal surface of vascular endothelium (By similarity).[1] [2]
Publication Abstract from PubMed
Lipoprotein lipase (LPL) is responsible for the intravascular processing of triglyceride-rich lipoproteins. The LPL within capillaries is bound to GPIHBP1, an endothelial cell protein with a three-fingered LU domain and an N-terminal intrinsically disordered acidic domain. Loss-of-function mutations in LPL or GPIHBP1 cause severe hypertriglyceridemia (chylomicronemia), but structures for LPL and GPIHBP1 have remained elusive. Inspired by our recent discovery that GPIHBP1's acidic domain preserves LPL structure and activity, we crystallized an LPL-GPIHBP1 complex and solved its structure. GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interactions. Analysis of electrostatic surfaces revealed that LPL contains a large basic patch spanning its N- and C-terminal domains. GPIHBP1's acidic domain was not defined in the electron density map but was positioned to interact with LPL's large basic patch, providing a likely explanation for how GPIHBP1 stabilizes LPL. The LPL-GPIHBP1 structure provides insights into mutations causing chylomicronemia.
Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis.,Birrane G, Beigneux AP, Dwyer B, Strack-Logue B, Kristensen KK, Francone OL, Fong LG, Mertens HDT, Pan CQ, Ploug M, Young SG, Meiyappan M Proc Natl Acad Sci U S A. 2018 Dec 17. pii: 1817984116. doi:, 10.1073/pnas.1817984116. PMID:30559189[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lutz EP, Merkel M, Kako Y, Melford K, Radner H, Breslow JL, Bensadoun A, Goldberg IJ. Heparin-binding defective lipoprotein lipase is unstable and causes abnormalities in lipid delivery to tissues. J Clin Invest. 2001 May;107(9):1183-92. doi: 10.1172/JCI11774. PMID:11342582 doi:http://dx.doi.org/10.1172/JCI11774
- ↑ Pingitore P, Lepore SM, Pirazzi C, Mancina RM, Motta BM, Valenti L, Berge KE, Retterstol K, Leren TP, Wiklund O, Romeo S. Identification and characterization of two novel mutations in the LPL gene causing type I hyperlipoproteinemia. J Clin Lipidol. 2016 Jul-Aug;10(4):816-823. doi: 10.1016/j.jacl.2016.02.015. Epub, 2016 Mar 10. PMID:27578112 doi:http://dx.doi.org/10.1016/j.jacl.2016.02.015
- ↑ Birrane G, Beigneux AP, Dwyer B, Strack-Logue B, Kristensen KK, Francone OL, Fong LG, Mertens HDT, Pan CQ, Ploug M, Young SG, Meiyappan M. Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis. Proc Natl Acad Sci U S A. 2018 Dec 17. pii: 1817984116. doi:, 10.1073/pnas.1817984116. PMID:30559189 doi:http://dx.doi.org/10.1073/pnas.1817984116
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