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6oau

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Current revision

Apo Structure of WT Lipoprotein Lipase in Complex with GPIHBP1 Mutant N78D N82D produced in GnTI-deficient HEK293-F cells

Structural highlights

6oau is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.48Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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) plays a central role in triglyceride (TG) metabolism. By catalyzing the hydrolysis of TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating TG and TRL concentrations. Until very recently, structural information for LPL was limited to homology models, presumably due to the propensity of LPL to unfold and aggregate. By coexpressing LPL with a soluble variant of its accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and with its chaperone protein lipase maturation factor 1 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure determination. We report here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5-3.0 A resolution, including a structure with a novel inhibitor bound to LPL. Binding of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled determination of the first crystal structure of LPL that includes these important regions of the protein. It was assumed for many years that LPL was only active as a homodimer. The structures and additional biochemical data reported here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomeric 1:1 complex. The crystal structures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.

Structure of lipoprotein lipase in complex with GPIHBP1.,Arora R, Nimonkar AV, Baird D, Wang C, Chiu CH, Horton PA, Hanrahan S, Cubbon R, Weldon S, Tschantz WR, Mueller S, Brunner R, Lehr P, Meier P, Ottl J, Voznesensky A, Pandey P, Smith TM, Stojanovic A, Flyer A, Benson TE, Romanowski MJ, Trauger JW Proc Natl Acad Sci U S A. 2019 May 21;116(21):10360-10365. doi:, 10.1073/pnas.1820171116. Epub 2019 May 9. PMID:31072929^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Arora R, Nimonkar AV, Baird D, Wang C, Chiu CH, Horton PA, Hanrahan S, Cubbon R, Weldon S, Tschantz WR, Mueller S, Brunner R, Lehr P, Meier P, Ottl J, Voznesensky A, Pandey P, Smith TM, Stojanovic A, Flyer A, Benson TE, Romanowski MJ, Trauger JW. Structure of lipoprotein lipase in complex with GPIHBP1. Proc Natl Acad Sci U S A. 2019 May 21;116(21):10360-10365. doi:, 10.1073/pnas.1820171116. Epub 2019 May 9. PMID:31072929 doi:http://dx.doi.org/10.1073/pnas.1820171116

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6oau"

@@ Line 3: / Line 3: @@
 <StructureSection load='6oau' size='340' side='right'caption='[[6oau]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6oau]] 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=6OAU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OAU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6oau]] 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=6OAU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OAU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 2.48&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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=6oau FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oau OCA], [https://pdbe.org/6oau PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oau RCSB], [https://www.ebi.ac.uk/pdbsum/6oau PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oau 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=6oau FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oau OCA], [http://pdbe.org/6oau PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oau RCSB], [http://www.ebi.ac.uk/pdbsum/6oau PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oau ProSAT]</span></td></tr>
 </table>
 == 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 ==
-[[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;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 </div>
 <div class="pdbe-citations 6oau" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Lipase 3D Structures|Lipase 3D Structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lipoprotein lipase]]
+[[Category: Arora R]]
-[[Category: Arora, R]]
+[[Category: Benson TE]]
-[[Category: Benson, T E]]
+[[Category: Horton PA]]
-[[Category: Horton, P A]]
+[[Category: Romanowski MJ]]
-[[Category: Romanowski, M J]]
-[[Category: Hydrolase-protein binding complex]]
-[[Category: Lipase]]

6oau

From Proteopedia

Current revision

Apo Structure of WT Lipoprotein Lipase in Complex with GPIHBP1 Mutant N78D N82D produced in GnTI-deficient HEK293-F cells

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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