Structural mechanism of protein recognition by the FW domain of autophagy receptor Nbr1

Zhang, Jianxiu; Wang, Yingying; Pan, Zhao-Qian; Li, Yulu; Sui, Jianhua; Du, Li-Lin; Ye, Keqiong

doi:10.1038/s41467-022-31439-5

Cited by 8 publications

(8 citation statements)

References 54 publications

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“…TmNbr1 contains 4 copies of the ZZ-type zinc-finger domain, similar to the Nbr1 homologs from filamentous fungi A. fumigatus, Chaetomium thermophilum and Sordaria macrospora . The four conserved tryptophan residues (FW) are a signature domain of Nbr1, playing an important role in protein binding and cargo recognition ( Zhang et al., 2022 ). The FW domains become degenerated in the fission yeast Nbr1 ( Zhang et al., 2022 ).…”

Section: Resultsmentioning

confidence: 99%

Antibody screening reveals antigenic proteins involved in Talaromyces marneffei and human interaction

Wangsanut

Amsri

Pongpom

2023

Front. Cell. Infect. Microbiol.

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Talaromycosis is a fungal infection that generally affects immunocompromised hosts and is one of the most frequent systemic mycoses in HIV patients, especially in endemic areas such as Southeast Asia. Talaromyces marneffei, the causative agent of talaromycosis, grows as a mold in the environment but adapts to the human body and host niches by transitioning from conidia to yeast-like cells. Knowledge of the human host and T. marneffei interaction has a direct impact on the diagnosis, yet studies are still lacking. The morbidity and mortality rates are high in taloromycosis patients if the diagnosis and treatments are delayed. Immunogenic proteins are excellent candidates for developing detection tools. Previously, we identified antigenic proteins that were recognized by antibodies from talaromycosis sera. Three of these identified proteins have been previously characterized in detail, while the others have not been explored. To expedite the progress of antigen discovery, the complete list of antigenic proteins and their features was fully reported in this study. Functional annotation and Gene Ontology examination revealed that these proteins showed a high association with membrane trafficking. Further bioinformatics analyses were performed to search for antigenic protein characteristics, including functional domains, critical residues, subcellular localization, secretory signals, and epitope peptide sequences. Expression profiling of these antigenic encoding genes was investigated using quantitative real-time PCR. The results demonstrated that most genes were expressed at low levels in the mold form, but were highly upregulated in the pathogenic yeast phase, consistent with the antigenic role of these genes during the human-host interaction. Most transcripts accumulated in the conidia, suggesting a role during phase transition. The collection of all antigen-encoding DNA sequences described here is freely accessible at GenBank, which could be useful for the research community to develop into biomarkers, diagnostic tests, research detection tools, and even vaccines.

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Section: Resultsmentioning

confidence: 99%

Antibody screening reveals antigenic proteins involved in Talaromyces marneffei and human interaction

Wangsanut

Amsri

Pongpom

2023

Front. Cell. Infect. Microbiol.

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“…The Atg19 and Atg34 ABD structures are very similar, with a root mean square difference (RMSD) of 2.1 Å for 102 residues, forming an immunoglobulin-like β-sandwich fold with two β-sheets, each with four antiparallel β-strands. The ABD of the NBR1 homolog of the filamentous fungus C. thermophilum has an FW domain very similar in structure to those found in human NBR1 and ILRUN ( Zhang et al, 2022a ). Structural comparison of FW domain structures of NBR1 and ILRUN with the ABD of Atg19 and Atg34 revealed the latter to be FW-like domains ( Fig.…”

Section: Atg19 and Atg34 Are Yeast Nbr1 Homologsmentioning

confidence: 89%

“…The FW domain of human NBR1 binds to microtubule-associated protein MAP1B and TAX1BP1 ( Marchbank et al, 2012 ; Turco et al, 2021 ). The recent finding that the FW domain of the filamentous fungus Chaetomium thermophilum binds specifically to vacuolar α-mannosidase (Ams1) and delivers Ams1 to the vacuole by autophagy in the fission yeast S. pombe shows that this domain can be involved in cargo recognition ( Zhang et al, 2022a ).…”

Section: Domain Structure Of Nbr1mentioning

confidence: 99%

NBR1: The archetypal selective autophagy receptor

Rasmussen

Kournoutis

Lamark

et al. 2022

Journal of Cell Biology

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NBR1 was discovered as an autophagy receptor not long after the first described vertebrate autophagy receptor p62/SQSTM1. Since then, p62 has currently been mentioned in >10,000 papers on PubMed, while NBR1 is mentioned in <350 papers. Nonetheless, evolutionary analysis reveals that NBR1, and likely also selective autophagy, was present already in the last eukaryotic common ancestor (LECA), while p62 appears first in the early Metazoan lineage. Furthermore, yeast-selective autophagy receptors Atg19 and Atg34 represent NBR1 homologs. NBR1 is the main autophagy receptor in plants that do not contain p62, while most animal taxa contain both NBR1 and p62. Mechanistic studies are starting to shed light on the collaboration between mammalian NBR1 and p62 in the autophagic degradation of protein aggregates (aggrephagy). Several domains of NBR1 are involved in cargo recognition, and the list of known substrates for NBR1-mediated selective autophagy is increasing. Lastly, roles of NBR1 in human diseases such as proteinopathies and cancer are emerging.

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“…Examples include the PB1, UBA, and ZZ domains of p62 (Fig. 6C, left box) [183][184][185]; the PB1, UBA, and FW domains of NBR1 [186][187][188]; the SKICH and UBZ domains of TAX1BP1 [189,190]; the UBAN and UBZ domains of Optineurin [191][192][193]; the SKICH and UBZ domains of NDP52/CAL-COCO2 [36,194]; the ABD and coiled-coil domains of Atg19 [195,196]; the ABD domain of Atg34 [195]; and the pseudo-receiver domain of Atg32 (Fig. 6C, right box) [197].…”

Section: Structural Studies On Sarsmentioning

confidence: 99%

Structural view on autophagosome formation

Noda

2023

FEBS Letters

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Autophagy is a conserved intracellular degradation system in eukaryotes, involving the sequestration of degradation targets into autophagosomes, which are subsequently delivered to lysosomes (or vacuoles in yeasts and plants) for degradation. In budding yeast, starvation‐induced autophagosome formation relies on approximately 20 core Atg proteins, grouped into six functional categories: the Atg1/ULK complex, the phosphatidylinositol‐3 kinase complex, the Atg9 transmembrane protein, the Atg2–Atg18/WIPI complex, the Atg8 lipidation system, and the Atg12–Atg5 conjugation system. Additionally, selective autophagy requires cargo receptors and other factors, including a fission factor, for specific sequestration. This review covers the 30‐year history of structural studies on core Atg proteins and factors involved in selective autophagy, examining X‐ray crystallography, NMR, and cryo‐EM techniques. The molecular mechanisms of autophagy are explored based on protein structures, and future directions in the structural biology of autophagy are discussed, considering the advancements in the era of AlphaFold.

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Structural mechanism of protein recognition by the FW domain of autophagy receptor Nbr1

Cited by 8 publications

References 54 publications

Antibody screening reveals antigenic proteins involved in Talaromyces marneffei and human interaction

Antibody screening reveals antigenic proteins involved in Talaromyces marneffei and human interaction

NBR1: The archetypal selective autophagy receptor

Structural view on autophagosome formation

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