View source for 4uf9


==Electron cryo-microscopy structure of PB1-p62 type T filaments==
<SX load='4uf9' size='340' side='right' viewer='molstar' caption='[[4uf9]], [[Resolution|resolution]] 10.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4uf9]] is a 3 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=4UF9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UF9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 10.3&#8491;</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=4uf9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf9 OCA], [https://pdbe.org/4uf9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uf9 RCSB], [https://www.ebi.ac.uk/pdbsum/4uf9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uf9 ProSAT]</span></td></tr>
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== Disease ==
[https://www.uniprot.org/uniprot/SQSTM_HUMAN SQSTM_HUMAN] Defects in SQSTM1 are a cause of Paget disease of bone (PDB) [MIM:[https://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 ==
[https://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> 
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== Publication Abstract from PubMed ==
The scaffold protein p62/SQSTM1 is involved in protein turnover and signaling and is commonly found in dense protein bodies in eukaryotic cells. In autophagy, p62 acts as a selective autophagy receptor that recognizes and shuttles ubiquitinated proteins to the autophagosome for degradation. The structural organization of p62 in cellular bodies and the interplay of these assemblies with ubiquitin and the autophagic marker LC3 remain to be elucidated. Here, we present a cryo-EM structural analysis of p62. Together with structures of assemblies from the PB1 domain, we show that p62 is organized in flexible polymers with the PB1 domain constituting a helical scaffold. Filamentous p62 is capable of binding LC3 and addition of long ubiquitin chains induces disassembly and shortening of filaments. These studies explain how p62 assemblies provide a large molecular scaffold for the nascent autophagosome and reveal how they can bind ubiquitinated cargo.

The Selective Autophagy Receptor p62 Forms a Flexible Filamentous Helical Scaffold.,Ciuffa R, Lamark T, Tarafder AK, Guesdon A, Rybina S, Hagen WJ, Johansen T, Sachse C Cell Rep. 2015 May 5;11(5):748-58. doi: 10.1016/j.celrep.2015.03.062. Epub 2015, Apr 23. PMID:25921531<ref>PMID:25921531</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4uf9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sequestosome|Sequestosome]]
== References ==
<references/>
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</SX>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ciuffa R]]
[[Category: Guesdon A]]
[[Category: Hagen WJH]]
[[Category: Johansen T]]
[[Category: Lamark T]]
[[Category: Rybina S]]
[[Category: Sachse C]]
[[Category: Tarafder A]]