The NMR structure of the p62 PB1 domain, a key protein in autophagy and NF-κB signaling pathway
In eukaryotic cells, proteins are degraded via two main pathways; One is the ubiquitin-proteasome system that degrades short-lived proteins, and the other is autophagy that degrades long-lived proteins and damaged organelles (Noda et al. 2009). The p62, also called ZIP (PKC-ζ-interacting protein) or sequestosome 1, plays a crucial role in these protein degradation pathways (Sumimoto et al. 2007). In autophagy, polyubiquitinated aggregated proteins and damaged organelles are enclosed by the isolation membrane, eventually enwrapped by the autophagosome. The autophagosome is fused with the vacuole/lysosome and its inner content is delivered and then degraded. The p62, initially identified as a protein that binds to the SH2 domain of the tyrosine kinase Lck, functions as a receptor protein for aberrant proteins. It contains a PB1 domain at its N terminus, followed by a ZZ-type zinc-finger motif, a LC3 interacting region, and a UBA domain at its C-terminus (Geetha and...
KeywordsElectrostatic Surface Potential D67A Mutant Conserve Lysine Residue HRV3C Protease Sedimentation Velocity Analytical Ultracentrifugation
This work was supported by Grant-in-Aid for Scientific Research (Kiban S) and the National Projects on Targeted Proteins Research Programs (TPRP) from Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
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