National Natural Science Foundation of China (NSFC)
32071199, 91940302
中国
Chinese Academy of Sciences
XDB37010201
中国
National Basic Research Program of China (973 Program)
2017YFA0504600
中国
引用
ジャーナル: EMBO J / 年: 2021 タイトル: Molecular and structural mechanisms of ZZ domain-mediated cargo selection by Nbr1. 著者: Ying-Ying Wang / Jianxiu Zhang / Xiao-Man Liu / Yulu Li / Jianhua Sui / Meng-Qiu Dong / Keqiong Ye / Li-Lin Du / 要旨: In selective autophagy, cargo selectivity is determined by autophagy receptors. However, it remains scarcely understood how autophagy receptors recognize specific protein cargos. In the fission yeast ...In selective autophagy, cargo selectivity is determined by autophagy receptors. However, it remains scarcely understood how autophagy receptors recognize specific protein cargos. In the fission yeast Schizosaccharomyces pombe, a selective autophagy pathway termed Nbr1-mediated vacuolar targeting (NVT) employs Nbr1, an autophagy receptor conserved across eukaryotes including humans, to target cytosolic hydrolases into the vacuole. Here, we identify two new NVT cargos, the mannosidase Ams1 and the aminopeptidase Ape4, that bind competitively to the first ZZ domain of Nbr1 (Nbr1-ZZ1). High-resolution cryo-EM analyses reveal how a single ZZ domain recognizes two distinct protein cargos. Nbr1-ZZ1 not only recognizes the N-termini of cargos via a conserved acidic pocket, similar to other characterized ZZ domains, but also engages additional parts of cargos in a cargo-specific manner. Our findings unveil a single-domain bispecific mechanism of autophagy cargo recognition, elucidate its underlying structural basis, and expand the understanding of ZZ domain-mediated protein-protein interactions.
タンパク質・ペプチド: Aspartyl aminopeptidase 1,ZZ-type zinc finger-containing protein P35G2.11c,Maltose/maltodextrin-binding periplasmic protein
リガンド: ZINC ION
リガンド: water
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超分子 #1: Ape4 and Nbr1 fusion protein
超分子
名称: Ape4 and Nbr1 fusion protein / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 詳細: The fusion protein comprises of the full-length Ape4, a linker sequence (GFKKASSSDNKEQ), residues 53-129 of Nbr1, and maltose binding protein (MBP).
由来(天然)
生物種: Schizosaccharomyces pombe 972h- (分裂酵母)
分子量
理論値: 750 KDa
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分子 #1: Aspartyl aminopeptidase 1,ZZ-type zinc finger-containing protein ...
分子
名称: Aspartyl aminopeptidase 1,ZZ-type zinc finger-containing protein P35G2.11c,Maltose/maltodextrin-binding periplasmic protein タイプ: protein_or_peptide / ID: 1 詳細: The fusion protein comprises of the full-length Ape4, a linker sequence (GFKKASSSDNKEQ), residues 53-129 of Nbr1, and maltose binding protein (MBP). コピー数: 12 / 光学異性体: LEVO / EC番号: aspartyl aminopeptidase