Journal
AUTOPHAGY
Volume 19, Issue 4, Pages 1359-1360Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2022.2123636
Keywords
Ams1; autophagy receptor; FW domain; Nbr1; selective autophagy
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In selective macroautophagy, autophagy receptors play a crucial role in determining cargo specificity. Most autophagy receptors are found only in certain eukaryotic lineages, except for Nbr1 proteins, which are conserved across eukaryotes. Our study discovered that the FW domain in the Nbr1 protein of Chaetomium thermophilum can bind to the autophagy cargo alpha-mannosidase Ams1, and this binding promotes the autophagic delivery of Ams1 into vacuoles. We also revealed the structural mechanism of Ams1 recognition by the FW domain through solving the structure of the FW-Ams1 complex.
In selective macroautophagy/autophagy, autophagy receptors are key molecules that determine cargo specificity. Most known autophagy receptors only exist in some but not all eukaryotic lineages. The exception is Nbr1 proteins, which are conserved across eukaryotes. The four-tryptophan (FW) domain is the hallmark of Nbr1 proteins, but its function has been unknown. Our recent study found that the FW domain in the Nbr1 protein of the filamentous fungus Chaetomium thermophilum binds the alpha-mannosidase Ams1, a known selective autophagy cargo in budding yeast and fission yeast. Furthermore, we showed that when C. thermophilum Nbr1 and Ams1 are expressed heterologously in fission yeast, FW domain-mediated binding can promote autophagic delivery of Ams1 into vacuoles. We solved the structure of the FW-Ams1 complex and revealed the structural mechanism underlying Ams1 recognition by the FW domain. The N-terminal di-glycine peptide of Ams1 fits into a conserved pocket of the FW domain. We propose that this cargo-binding mechanism may also be employed by Nbr1 proteins in other eukaryotes.
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