| Structural highlights
Disease
[GRP78_HUMAN] Note=Autoantigen in rheumatoid arthritis.[1]
Function
[GRP78_HUMAN] Probably plays a role in facilitating the assembly of multimeric protein complexes inside the ER.[2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Corrigall VM, Bodman-Smith MD, Fife MS, Canas B, Myers LK, Wooley P, Soh C, Staines NA, Pappin DJ, Berlo SE, van Eden W, van Der Zee R, Lanchbury JS, Panayi GS. The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis. J Immunol. 2001 Feb 1;166(3):1492-8. PMID:11160188
- ↑ Dana RC, Welch WJ, Deftos LJ. Heat shock proteins bind calcitonin. Endocrinology. 1990 Jan;126(1):672-4. PMID:2294010
- ↑ Kwon DH, Park OH, Kim L, Jung YO, Park Y, Jeong H, Hyun J, Kim YK, Song HK. Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter. Nat Commun. 2018 Aug 17;9(1):3291. doi: 10.1038/s41467-018-05825-x. PMID:30120248 doi:http://dx.doi.org/10.1038/s41467-018-05825-x
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