National Natural Science Foundation of China (NSFC)
32071199, 91940302
China
Chinese Academy of Sciences
XDB37010201
China
National Basic Research Program of China (973 Program)
2017YFA0504600
China
Citation
Journal: EMBO J / Year: 2021 Title: Molecular and structural mechanisms of ZZ domain-mediated cargo selection by Nbr1. Authors: Ying-Ying Wang / Jianxiu Zhang / Xiao-Man Liu / Yulu Li / Jianhua Sui / Meng-Qiu Dong / Keqiong Ye / Li-Lin Du / Abstract: 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.
History
Deposition
Oct 28, 2020
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Header (metadata) release
Jul 14, 2021
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Map release
Jul 14, 2021
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Update
May 29, 2024
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Current status
May 29, 2024
Processing site: PDBj / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Protein or peptide: Aspartyl aminopeptidase 1,ZZ-type zinc finger-containing protein P35G2.11c,Maltose/maltodextrin-binding periplasmic protein
Ligand: ZINC ION
Ligand: water
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Supramolecule #1: Ape4 and Nbr1 fusion protein
Supramolecule
Name: Ape4 and Nbr1 fusion protein / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: The fusion protein comprises of the full-length Ape4, a linker sequence (GFKKASSSDNKEQ), residues 53-129 of Nbr1, and maltose binding protein (MBP).
Source (natural)
Organism: Schizosaccharomyces pombe 972h- (yeast)
Molecular weight
Theoretical: 750 KDa
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Macromolecule #1: Aspartyl aminopeptidase 1,ZZ-type zinc finger-containing protein ...
Macromolecule
Name: Aspartyl aminopeptidase 1,ZZ-type zinc finger-containing protein P35G2.11c,Maltose/maltodextrin-binding periplasmic protein type: protein_or_peptide / ID: 1 Details: The fusion protein comprises of the full-length Ape4, a linker sequence (GFKKASSSDNKEQ), residues 53-129 of Nbr1, and maltose binding protein (MBP). Number of copies: 12 / Enantiomer: LEVO / EC number: aspartyl aminopeptidase
Model: Homemade / Material: GOLD / Mesh: 400 / Support film - topology: HOLEY ARRAY / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 60 sec.
Vitrification
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 5 seconds before plunging.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Specialist optics
Energy filter - Name: GIF Tridiem 4K / Energy filter - Slit width: 20 eV
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number real images: 1799 / Average exposure time: 5.4 sec. / Average electron dose: 50.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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