4ne9

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==PCSK9 in complex with LDLR peptide==
==PCSK9 in complex with LDLR peptide==
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<StructureSection load='4ne9' size='340' side='right' caption='[[4ne9]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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<StructureSection load='4ne9' size='340' side='right'caption='[[4ne9]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4ne9]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NE9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NE9 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4ne9]] is a 5 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=4NE9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NE9 FirstGlance]. <br>
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</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2p4e|2p4e]]</td></tr>
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<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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<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=4ne9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ne9 OCA], [http://pdbe.org/4ne9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ne9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ne9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ne9 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ne9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ne9 OCA], [https://pdbe.org/4ne9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ne9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ne9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ne9 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[http://omim.org/entry/603776 603776]]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref> [[http://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:[http://omim.org/entry/143890 143890]]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).<ref>PMID:3263645</ref> <ref>PMID:2569482</ref> <ref>PMID:3955657</ref> <ref>PMID:8347689</ref> <ref>PMID:2318961</ref> <ref>PMID:1446662</ref> <ref>PMID:1867200</ref> <ref>PMID:8462973</ref> <ref>PMID:8168830</ref> <ref>PMID:2726768</ref> <ref>PMID:1464748</ref> <ref>PMID:7573037</ref> <ref>PMID:7583548</ref> <ref>PMID:7550239</ref> <ref>PMID:7635461</ref> <ref>PMID:7635482</ref> <ref>PMID:7649546</ref> <ref>PMID:7649549</ref> <ref>PMID:8740918</ref> <ref>PMID:8664907</ref> <ref>PMID:9026534</ref> <ref>PMID:9254862</ref> <ref>PMID:9143924</ref> <ref>PMID:9259195</ref> <ref>PMID:9104431</ref> <ref>PMID:9654205</ref> <ref>PMID:9452094</ref> <ref>PMID:9452095</ref> <ref>PMID:9452118</ref> <ref>PMID:10206683</ref> <ref>PMID:10660340</ref> [:]<ref>PMID:9852677</ref> <ref>PMID:9678702</ref> <ref>PMID:10422803</ref> <ref>PMID:10090484</ref> <ref>PMID:10447263</ref> <ref>PMID:10978268</ref> <ref>PMID:10980548</ref> <ref>PMID:10882754</ref> <ref>PMID:11298688</ref> <ref>PMID:17142622</ref> <ref>PMID:19319977</ref> <ref>PMID:22160468</ref>
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[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN] Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3) [MIM:[https://omim.org/entry/603776 603776]. A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:12730697</ref>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN]] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref> [[http://www.uniprot.org/uniprot/LDLR_HUMAN LDLR_HUMAN]] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
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[https://www.uniprot.org/uniprot/PCSK9_HUMAN PCSK9_HUMAN] Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.<ref>PMID:17461796</ref> <ref>PMID:18197702</ref> <ref>PMID:18660751</ref> <ref>PMID:18039658</ref> <ref>PMID:22074827</ref> <ref>PMID:22580899</ref> <ref>PMID:22493497</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Liu, S]]
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[[Category: Homo sapiens]]
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[[Category: Autocatalytic cleavage]]
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[[Category: Large Structures]]
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[[Category: Cholesterol metabolism]]
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[[Category: Liu S]]
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[[Category: Hydrolase]]
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[[Category: Ldl receptor]]
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[[Category: Pcsk9]]
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Current revision

PCSK9 in complex with LDLR peptide

PDB ID 4ne9

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