5yp7
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Zinc binding protein== | |
| + | <StructureSection load='5yp7' size='340' side='right' caption='[[5yp7]], [[Resolution|resolution]] 1.42Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5yp7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YP7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YP7 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5yp7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yp7 OCA], [http://pdbe.org/5yp7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yp7 RCSB], [http://www.ebi.ac.uk/pdbsum/5yp7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yp7 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/SQSTM_HUMAN SQSTM_HUMAN]] Defects in SQSTM1 are a cause of Paget disease of bone (PDB) [MIM:[http://omim.org/entry/602080 602080]]. PDB is a metabolic bone disease affecting the axial skeleton and characterized by focal areas of increased and disorganized bone turn-over due to activated osteoclasts. Manifestations of the disease include bone pain, deformity, pathological fractures, deafness, neurological complications and increased risk of osteosarcoma. PDB is a chronic disease affecting 2 to 3% of the population above the age of 40 years.<ref>PMID:19931284</ref> <ref>PMID:11992264</ref> <ref>PMID:12374763</ref> <ref>PMID:14584883</ref> <ref>PMID:15146436</ref> <ref>PMID:15207768</ref> <ref>PMID:15125799</ref> <ref>PMID:15176995</ref> Note=In a cell model for Huntington disease (HD), appears to form a shell surrounding aggregates of mutant HTT that may protect cells from apoptosis, possibly by recruiting autophagosomal components to the polyubiquitinylated protein aggregates.<ref>PMID:16286508</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/SQSTM_HUMAN SQSTM_HUMAN]] Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures). Links ALIS to the autophagic machinery via direct interaction with MAP1 LC3 family members. May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels.<ref>PMID:10356400</ref> <ref>PMID:10747026</ref> <ref>PMID:11244088</ref> <ref>PMID:12471037</ref> <ref>PMID:15340068</ref> <ref>PMID:16079148</ref> <ref>PMID:16286508</ref> <ref>PMID:15953362</ref> <ref>PMID:15911346</ref> <ref>PMID:15802564</ref> <ref>PMID:19931284</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | p62/SQSTM1 is the key autophagy adapter protein and the hub of multi-cellular signaling. It was recently reported that autophagy and N-end rule pathways are linked via p62. However, the exact recognition mode of degrading substrates and regulation of p62 in the autophagic pathway remain unknown. Here, we present the complex structures between the ZZ-domain of p62 and various type-1 and type-2 N-degrons. The binding mode employed in the interaction of the ZZ-domain with N-degrons differs from that employed by classic N-recognins. It was also determined that oligomerization via the PB1 domain can control functional affinity to the R-BiP substrate. Unexpectedly, we found that self-oligomerization and disassembly of p62 are pH-dependent. These findings broaden our understanding of the functional repertoire of the N-end rule pathway and provide an insight into the regulation of p62 during the autophagic pathway. | ||
| - | + | Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter.,Kwon DH, Park OH, Kim L, Jung YO, Park Y, Jeong H, Hyun J, Kim YK, Song HK Nat Commun. 2018 Aug 17;9(1):3291. doi: 10.1038/s41467-018-05825-x. PMID:30120248<ref>PMID:30120248</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5yp7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Kim, L]] | ||
| + | [[Category: Kwon, D H]] | ||
| + | [[Category: Song, H K]] | ||
| + | [[Category: Autophagy]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: N-end rule]] | ||
| + | [[Category: P62/sqstm1]] | ||
| + | [[Category: Signaling protein]] | ||
| + | [[Category: Zz domain]] | ||
Revision as of 07:18, 29 August 2018
Zinc binding protein
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Categories: Kim, L | Kwon, D H | Song, H K | Autophagy | Complex | N-end rule | P62/sqstm1 | Signaling protein | Zz domain
