Structural basis of target recognition by Atg8/LC3 during selective autophagy.

摘要: Autophagy is a non-selective bulk degradation process in which isolation membranes enclose portion of cytoplasm to form double-membrane vesicles, called autophagosomes, and deliver their inner constituents the lytic compartments. Recent studies have also shed light on another mode autophagy that selectively degrades various targets. Yeast Atg8 its mammalian homologue LC3 are ubiquitin-like modifiers localized play crucial roles formation autophagosomes. These proteins involved selective incorporation specific cargo molecules into interact with Atg19 p62, receptor for vacuolar enzymes disease-related protein aggregates, respectively. Using X-ray crystallography NMR, we herein report structural basis Atg8–Atg19 LC3–p62 interactions. Remarkably, were shown respectively, quite similar manner: they recognized side-chains Trp Leu four-amino acid motif, WXXL, p62 using hydrophobic pockets conserved among homologues. Together mutational analyses, our results show fundamental mechanism allows homologues, association WXXL-containing proteins, capture molecules, thereby endowing and/or assembly machineries target selectivity.