View source for 7anq


==Complete PCSK9 C-ter domain in complex with VHH P1.40==
<StructureSection load='7anq' size='340' side='right'caption='[[7anq]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7anq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6f5g 6f5g]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ANQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ANQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7anq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7anq OCA], [https://pdbe.org/7anq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7anq RCSB], [https://www.ebi.ac.uk/pdbsum/7anq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7anq ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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> 

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[PCSK9|PCSK9]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Ciccone L]]
[[Category: Dive V]]
[[Category: Fruchart Gaillard C]]
[[Category: Legrand P]]
[[Category: Seidahn NG]]
[[Category: Stura EA]]