6LAN

Structure of CCDC50 and LC3B complex

Summary for 6LAN

• Entry DOI: 10.2210/pdb6lan/pdb
• Descriptor: Coiled-coil domain-containing protein 50,Microtubule-associated proteins 1A/1B light chain 3B (2 entities in total)
• Functional Keywords: autophagy, complex, peptide binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 15883.15

Authors

Liu, L.,Li, J.,Hou, P. (deposition date: 2019-11-12, release date: 2020-09-30, Last modification date: 2023-11-22)

Primary citation

Hou, P.,Yang, K.,Jia, P.,Liu, L.,Lin, Y.,Li, Z.,Li, J.,Chen, S.,Guo, S.,Pan, J.,Wu, J.,Peng, H.,Zeng, W.,Li, C.,Liu, Y.,Guo, D.
A novel selective autophagy receptor, CCDC50, delivers K63 polyubiquitination-activated RIG-I/MDA5 for degradation during viral infection.
Cell Res., 31:62-79, 2021

PubMed Abstract: Autophagy is a conserved process that delivers cytosolic substances to the lysosome for degradation, but its direct role in the regulation of antiviral innate immunity remains poorly understood. Here, through high-throughput screening, we discovered that CCDC50 functions as a previously unknown autophagy receptor that negatively regulates the type I interferon (IFN) signaling pathway initiated by RIG-I-like receptors (RLRs), the sensors for RNA viruses. The expression of CCDC50 is enhanced by viral infection, and CCDC50 specifically recognizes K63-polyubiquitinated RLRs, thus delivering the activated RIG-I/MDA5 for autophagic degradation. The association of CCDC50 with phagophore membrane protein LC3 is confirmed by crystal structure analysis. In contrast to other known autophagic cargo receptors that associate with either the LIR-docking site (LDS) or the UIM-docking site (UDS) of LC3, CCDC50 can bind to both LDS and UDS, representing a new type of cargo receptor. In mouse models with RNA virus infection, CCDC50 deficiency reduces the autophagic degradation of RIG-I/MDA5 and promotes type I IFN responses, resulting in enhanced viral resistance and improved survival rates. These results reveal a new link between autophagy and antiviral innate immune responses and provide additional insights into the regulatory mechanisms of RLR-mediated antiviral signaling.

PubMed: 32612200
DOI: 10.1038/s41422-020-0362-1

Experimental method

X-RAY DIFFRACTION (1.41 Å)