| Structural highlights
Function
[NBR1_ARATH] Autophagic substrate degraded in the vacuole by non-selective autophagy. Requires ATG8 protein expression to be recognized as an autophagic substrate (PubMed:21606687). Acts probably as a receptor for autophagosomal degradation of ubiquitinated proteins. Targets ubiquitinated protein aggregates derived from denatured or damaged non-native proteins generated under stress conditions (PubMed:23341779). Functions additively with the E3 ubiquitin-protein ligase CHIP for autophagosomal degradation of proteotoxic aggregates formed under stress conditions (PubMed:24497840).[1] [2] [3]
Publication Abstract from PubMed
p62/SQSTM1 is an autophagy receptor and signaling adaptor with an N-terminal PB1 domain that forms the scaffold of phase-separated p62 bodies in the cell. The molecular determinants that govern PB1 domain filament formation in vitro remain to be determined and the role of p62 filaments inside the cell is currently unclear. We here determine four high-resolution cryo-EM structures of different human and Arabidopsis PB1 domain assemblies and observed a filamentous ultrastructure of p62/SQSTM1 bodies using correlative cellular EM. We show that oligomerization or polymerization, driven by a double arginine finger in the PB1 domain, is a general requirement for lysosomal targeting of p62. Furthermore, the filamentous assembly state of p62 is required for autophagosomal processing of the p62-specific cargo KEAP1. Our results show that using such mechanisms, p62 filaments can be critical for cargo uptake in autophagy and are an integral part of phase-separated p62 bodies.
Structural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake.,Jakobi AJ, Huber ST, Mortensen SA, Schultz SW, Palara A, Kuhm T, Shrestha BK, Lamark T, Hagen WJH, Wilmanns M, Johansen T, Brech A, Sachse C Nat Commun. 2020 Jan 23;11(1):440. doi: 10.1038/s41467-020-14343-8. PMID:31974402[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Svenning S, Lamark T, Krause K, Johansen T. Plant NBR1 is a selective autophagy substrate and a functional hybrid of the mammalian autophagic adapters NBR1 and p62/SQSTM1. Autophagy. 2011 Sep;7(9):993-1010. doi: 10.4161/auto.7.9.16389. Epub 2011 Sep 1. PMID:21606687 doi:http://dx.doi.org/10.4161/auto.7.9.16389
- ↑ Zhou J, Wang J, Cheng Y, Chi YJ, Fan B, Yu JQ, Chen Z. NBR1-mediated selective autophagy targets insoluble ubiquitinated protein aggregates in plant stress responses. PLoS Genet. 2013;9(1):e1003196. doi: 10.1371/journal.pgen.1003196. Epub 2013 Jan , 17. PMID:23341779 doi:http://dx.doi.org/10.1371/journal.pgen.1003196
- ↑ Zhou J, Zhang Y, Qi J, Chi Y, Fan B, Yu JQ, Chen Z. E3 ubiquitin ligase CHIP and NBR1-mediated selective autophagy protect additively against proteotoxicity in plant stress responses. PLoS Genet. 2014 Jan 30;10(1):e1004116. doi: 10.1371/journal.pgen.1004116., eCollection 2014 Jan. PMID:24497840 doi:http://dx.doi.org/10.1371/journal.pgen.1004116
- ↑ Jakobi AJ, Huber ST, Mortensen SA, Schultz SW, Palara A, Kuhm T, Shrestha BK, Lamark T, Hagen WJH, Wilmanns M, Johansen T, Brech A, Sachse C. Structural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake. Nat Commun. 2020 Jan 23;11(1):440. doi: 10.1038/s41467-020-14343-8. PMID:31974402 doi:http://dx.doi.org/10.1038/s41467-020-14343-8
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