NDLI: Structural basis for sorting mechanism of p62 in selective autophagy.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sou, Yu-shin Tanaka, Keiji Ezaki, Junji Kominami, Eiki Komatsu, Masaaki Kumanomidou, Taichi Ueno, Takashi Ichimura, Yoshinobu Mizushima, Tsunehiro Yamane, Takashi
Description	Author Affiliation: Ichimura Y ( Department of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421.)
Abstract	Impairment of autophagic degradation of the ubiquitin- and LC3-binding protein 'p62' leads to the formation of cytoplasmic inclusion bodies. However, little is known about the sorting mechanism of p62 to autophagic degradation. Here we identified a motif of murine p62 consisting of 11 amino acids (Ser334-Ser344) containing conserved acidic and hydrophobic residues across species, as an LC3 recognition sequence (LRS). The crystal structure of the LC3-LRS complex at 1.56 angstroms resolution revealed interaction of Trp340 and Leu343 of p62 with different hydrophobic pockets on the ubiquitin fold of LC3. In vivo analyses demonstrated that p62 mutants lacking LC3 binding ability accumulated without entrapping into autophagosomes in the cytoplasm and subsequently formed ubiquitin-positive inclusion bodies as in autophagy-deficient cells. These results demonstrate that the intracellular level of p62 is tightly regulated by autophagy through the direct interaction of LC3 with p62 and reveal that selective turnover of p62 via autophagy controls inclusion body formation.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	33
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adaptor Proteins, Signal Transducing Physiology Autophagy Chemistry Genetics Binding Sites Carrier Proteins Lysosomes Maltose-Binding Proteins Microtubule-Associated Proteins Recombinant Fusion Proteins Metabolism Sequence Deletion Vacuoles Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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