7D0E

Crystal structure of FIP200 Claw/p-CCPG1 FIR2

Summary for 7D0E

• Entry DOI: 10.2210/pdb7d0e/pdb
• Descriptor: RB1-inducible coiled-coil protein 1, Cell cycle progression protein 1 FIR2, 3-(2-hydroxyethyloxy)-2-[2-(2-hydroxyethyloxy)ethoxymethyl]-2-(2-hydroxyethyloxymethyl)propan-1-ol, ... (5 entities in total)
• Functional Keywords: autophagy, fip200, ccpg1, signaling protein, signaling protein-protein binding complex, signaling protein/protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 13954.93

Authors

Zhou, Z.X.,Pan, L.F. (deposition date: 2020-09-09, release date: 2021-03-31, Last modification date: 2024-11-13)

Primary citation

Zhou, Z.,Liu, J.,Fu, T.,Wu, P.,Peng, C.,Gong, X.,Wang, Y.,Zhang, M.,Li, Y.,Wang, Y.,Xu, X.,Li, M.,Pan, L.
Phosphorylation regulates the binding of autophagy receptors to FIP200 Claw domain for selective autophagy initiation.
Nat Commun, 12:1570-1570, 2021

PubMed Abstract: The ULK complex initiates the autophagosome formation, and has recently been implicated in selective autophagy by interacting with autophagy receptors through its FIP200 subunit. However, the structural mechanism underlying the interactions of autophagy receptors with FIP200 and the relevant regulatory mechanism remain elusive. Here, we discover that the interactions of FIP200 Claw domain with autophagy receptors CCPG1 and Optineurin can be regulated by the phosphorylation in their respective FIP200-binding regions. We determine the crystal structures of FIP200 Claw in complex with the phosphorylated CCPG1 and Optineurin, and elucidate the detailed molecular mechanism governing the interactions of FIP200 Claw with CCPG1 and Optineurin as well as their potential regulations by kinase-mediated phosphorylation. In addition, we define the consensus FIP200 Claw-binding motif, and find other autophagy receptors that contain this motif within their conventional LC3-interacting regions. In all, our findings uncover a general and phosphoregulatable binding mode shared by many autophagy receptors to interact with FIP200 Claw for autophagosome biogenesis, and are valuable for further understanding the molecular mechanism of selective autophagy.

PubMed: 33692357
DOI: 10.1038/s41467-021-21874-1

Experimental method

X-RAY DIFFRACTION (1.4 Å)