2ZJD

Crystal Structure of LC3-p62 complex

2ZJD の概要

• エントリーDOI: 10.2210/pdb2zjd/pdb
• 分子名称: Microtubule-associated proteins 1A/1B light chain 3B precursor, undecameric peptide from Sequestosome-1 (3 entities in total)
• 機能のキーワード: p62, autophagy, lc3, microtubule-associated protein 1 light chain 3, cytoplasm, cytoplasmic vesicle, lipoprotein, membrane, ubl conjugation pathway, alternative splicing, apoptosis, differentiation, endosome, immune response, metal-binding, nucleus, phosphoprotein, zinc, zinc-finger, apoptosis inhibitor-apoptosis complex, apoptosis inhibitor/apoptosis
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: Q9GZQ8; Cytoplasm: Q64337
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 32623.28

構造登録者

Ichimura, Y.,Kumanomidou, T.,Sou, Y.,Mizushima, T.,Ezaki, J.,Ueno, T.,Kominami, E.,Yamane, T.,Tanaka, K.,Komatsu, M. (登録日: 2008-03-05, 公開日: 2008-06-03, 最終更新日: 2023-11-01)

主引用文献

Ichimura, Y.,Kumanomidou, T.,Sou, Y.-S.,Mizushima, T.,Ezaki, J.,Ueno, T.,Kominami, E.,Yamane, T.,Tanaka, K.,Komatsu, M.
Structural Basis for Sorting Mechanism of p62 in Selective Autophagy
J.Biol.Chem., 283:22847-22857, 2008

PubMed 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.

PubMed: 18524774
DOI: 10.1074/jbc.M802182200

実験手法

X-RAY DIFFRACTION (1.56 Å)