On June 25, 2021, Dr. YE Keqiong's team at the Institute of Biophysics (IBP), Chinese Academy of Sciences and Dr. DU Li-Lin's team at the National Institute of Biological Sciences (NIBS), Beijing, published a collaborative study in Nature Communications entitled "Structural mechanism of protein recognition by the FW domain of autophagy receptor Nbr1". The study discovered how the four-tryptophan (FW) domain of autophagy receptor Nbr1 structurally recognizes a cargo protein.

Autophagy transports cytoplasmic materials to lysosomes and is important for cell homeostasis. Neighbor of BRCA1 (Nbr1) is a conserved autophagy receptor that specifically recognizes cargos in selective autophagy. Nbr1 proteins from different organisms contain a variable number of domains, but share a signature FW domain whose function remains unclear.

The newly published study found that Nbr1 from the filamentous fungus Chaetomium thermophilum uses its FW domain to bind the α-mannosidase Ams1 and delivers Ams1 to the vacuole by conventional autophagy in heterologous fission yeast. The structure of the Ams1-FW complex was determined at 2.2 Å resolution by cryo-electron microscopy. The FW domain simultaneously binds two subunits of Ams1 tetramer, hence recognizing its quaternary structure. The structure shows that the N-terminal di-glycine of Ams1 is specifically recognized by a conserved pocket of the FW domain. The peptide-binding pocket of the FW domain becomes degenerated in fission yeast Nbr1, which binds Ams1 with a ZZ domain instead. This study illustrates for the first time the protein binding mode of the FW domain and also reveals the versatility of Nbr1-mediated cargo recognition.

Figure. Cryo-EM structure of Ams1-Nbr1 FW complex

In the collaborative study, Prof. YE Keqiong at IBP and Prof. DU Li-Lin at NIBS were the corresponding authors. Dr. ZHANG Jianxiu at IBP and Drs. WANG Ying-Ying and PAN Zhao-Qian at NIBS were the co-first authors. The research was supported by National Natural Science Foundation of China, Strategic Priority Research Program of Chinese Academy of Sciences, National Key R&D Program of China, Chinese Ministry of Science and Technology and the Beijing municipal Government.

Full text link: https://doi.org/10.1038/s41467-022-31439-5

Contact: Ye Keqiong

Institute of Biophysics, Chinese Academy of Sciences

Beijing 100101, China

Email: yekeqiong@ibp.ac.cn

(Reported by Dr. Ye Keqiong's group)