3b0f: Difference between revisions

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/SQSTM_MOUSE SQSTM_MOUSE] 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. May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Adapter that mediates the interaction between TRAF6 and CYLD.<ref>PMID:14960283</ref> <ref>PMID:18382763</ref>  
[https://www.uniprot.org/uniprot/SQSTM_MOUSE SQSTM_MOUSE] 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. May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Adapter that mediates the interaction between TRAF6 and CYLD.<ref>PMID:14960283</ref> <ref>PMID:18382763</ref>  
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== Publication Abstract from PubMed ==
p62/SQSTM1/A170 is a multimodular protein that is found in ubiquitin-positive inclusions associated with neurodegenerative diseases. Recent findings indicate that p62 mediates the interaction between ubiquitinated proteins and autophagosomes, leading these proteins to be degraded via the autophagy-lysosomal pathway. This ubiquitin-mediated selective autophagy is thought to begin with recognition of the ubiquitinated proteins by the C-terminal ubiquitin-associated (UBA) domain of p62. We present here the crystal structure of the UBA domain of mouse p62 and the solution structure of its ubiquitin-bound form. The p62 UBA domain adopts a novel dimeric structure in crystals, which is distinctive from those of other UBA domains. NMR analyses reveal that in solution the domain exists in equilibrium between the dimer and monomer forms, and binding ubiquitin shifts the equilibrium toward the monomer to form a 1:1 complex between the UBA domain and ubiquitin. The dimer-to-monomer transition is associated with a structural change of the very C-terminal end of the p62 UBA domain, although the UBA fold itself is essentially maintained. Our data illustrate that dimerization and ubiquitin binding of the p62 UBA domain are incompatible with each other. These observations reveal an autoinhibitory mechanism in the p62 UBA domain and suggest that autoinhibition plays a role in the function of p62.
Crystal structure of the ubiquitin-associated (UBA) domain of p62 and its interaction with ubiquitin.,Isogai S, Morimoto D, Arita K, Unzai S, Tenno T, Hasegawa J, Sou YS, Komatsu M, Tanaka K, Shirakawa M, Tochio H J Biol Chem. 2011 Sep 9;286(36):31864-74. Epub 2011 Jun 29. PMID:21715324<ref>PMID:21715324</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
==See Also==

Latest revision as of 17:03, 13 March 2024

Crystal structure of the UBA domain of p62 and its interaction with ubiquitinCrystal structure of the UBA domain of p62 and its interaction with ubiquitin

Structural highlights

3b0f is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.4Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SQSTM_MOUSE 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. May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Adapter that mediates the interaction between TRAF6 and CYLD.[1] [2]

See Also

References

  1. ↑ Duran A, Serrano M, Leitges M, Flores JM, Picard S, Brown JP, Moscat J, Diaz-Meco MT. The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis. Dev Cell. 2004 Feb;6(2):303-9. PMID:14960283
  2. ↑ Jin W, Chang M, Paul EM, Babu G, Lee AJ, Reiley W, Wright A, Zhang M, You J, Sun SC. Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice. J Clin Invest. 2008 May;118(5):1858-66. doi: 10.1172/JCI34257. PMID:18382763 doi:10.1172/JCI34257

3b0f, resolution 1.40Å

Drag the structure with the mouse to rotate

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OCA
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