National Institute of Biological Sciences, Beijing, China.
Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Autophagy. 2023 Apr;19(4):1359-1360. doi: 10.1080/15548627.2022.2123636. Epub 2022 Sep 20.
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 binds the α-mannosidase Ams1, a known selective autophagy cargo in budding yeast and fission yeast. Furthermore, we showed that when 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 -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.
在选择性巨自噬/自噬中，自噬受体是决定货物特异性的关键分子。大多数已知的自噬受体仅存在于部分而不是所有真核生物谱系中。Nbr1 蛋白是一个例外，它在真核生物中是保守的。四色氨酸（FW）结构域是 Nbr1 蛋白的标志，但它的功能尚不清楚。我们最近的研究发现，丝状真菌中的 Nbr1 蛋白的 FW 结构域与 α-甘露糖苷酶 Ams1 结合，Ams1 是芽殖酵母和裂殖酵母中已知的选择性自噬货物。此外，我们表明，当 Nbr1 和 Ams1 在裂殖酵母中异源表达时，FW 结构域介导的结合可以促进 Ams1 进入液泡的自噬性递呈。我们解决了 FW-Ams1 复合物的结构，并揭示了 FW 结构域识别 Ams1 的结构机制。Ams1 的 -末端双甘氨酸肽适合 FW 结构域的一个保守口袋中。我们提出，这种货物结合机制也可能被其他真核生物中的 Nbr1 蛋白所采用。
