Structural Basis for Receptor-Mediated Selective Autophagy of Aminopeptidase I Aggregates.
Selective autophagy mediates the degradation of various cargoes, including protein aggregates and organelles, thereby contributing to cellular homeostasis. Cargo receptors ensure selectivity by tethering specific cargo to lipidated Atg8 at the isolation membrane. However, little is known about the structural requirements underlying receptor-mediated cargo recognition. Here, we report structural, biochemical, and cell biological analysis of the major selective cargo protein in budding yeast, aminopeptidase I (Ape1), and its complex with the receptor Atg19. The Ape1 propeptide has a trimeric coiled-coil structure, which tethers dodecameric Ape1 bodies together to form large aggregates. Atg19 disassembles the propeptide trimer and forms a 2:1 heterotrimer, which not only blankets the Ape1 aggregates but also regulates their size. These receptor activities may promote elongation of the isolation membrane along the aggregate surface, enabling sequestration of the cargo with high specificity.
Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan.
Akinori
A
Yamasaki
Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan.
Yasunori
Y
Watanabe
Department of Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo 001-0021, Japan.
Wakana
W
Adachi
Bioimaging Center, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8562, Japan.
Kuninori
K
Suzuki
Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan.
Kazuaki
K
Matoba
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
Hiromi
H
Kirisako
Department of Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo 001-0021, Japan.
Hiroyuki
H
Kumeta
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
Hitoshi
H
Nakatogawa
Unit for Cell Biology, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
Yoshinori
Y
Ohsumi
Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan; Department of Structural Biology, Faculty of Advanced Life Science, Hokkaido University, Sapporo 001-0021, Japan.
Fuyuhiko
F
Inagaki
Institute of Microbial Chemistry (BIKAKEN), Tokyo 141-0021, Japan. Electronic address: nn@bikaken.or.jp.
Nobuo N
NN
Noda
D000626:Aminopeptidases / Q000737:chemistry* / Q000378:metabolism*; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D066329:Protein Aggregates; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism*
C434480:ATG19 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D010455:Peptides; D066329:Protein Aggregates; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D000626:Aminopeptidases; C019689:APE1 protein, S cerevisiae