7WBB

Cryo-EM structure of substrate engaged Drg1 hexamer

Summary for 7WBB

• Entry DOI: 10.2210/pdb7wbb/pdb
• EMDB information: 32396
• Descriptor: AFG2 isoform 1, substrate, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total)
• Functional Keywords: cryo-em structure of drg1, ribosome, atp-binding protein
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Total number of polymer chains: 7
• Total formula weight: 516646.87

Authors

Ma, C.Y.,Wu, D.M.,Chen, Q.,Gao, N. (deposition date: 2021-12-16, release date: 2022-12-28, Last modification date: 2025-07-02)

Primary citation

Ma, C.,Wu, D.,Chen, Q.,Gao, N.
Structural dynamics of AAA + ATPase Drg1 and mechanism of benzo-diazaborine inhibition.
Nat Commun, 13:6765-6765, 2022

PubMed Abstract: The type II AAA + ATPase Drg1 is a ribosome assembly factor, functioning to release Rlp24 from the pre-60S particle just exported from nucleus, and its activity in can be inhibited by a drug molecule diazaborine. However, molecular mechanisms of Drg1-mediated Rlp24 removal and diazaborine-mediated inhibition are not fully understood. Here, we report Drg1 structures in different nucleotide-binding and benzo-diazaborine treated states. Drg1 hexamers transits between two extreme conformations (planar or helical arrangement of protomers). By forming covalent adducts with ATP molecules in both ATPase domain, benzo-diazaborine locks Drg1 hexamers in a symmetric and non-productive conformation to inhibits both inter-protomer and inter-ring communication of Drg1 hexamers. We also obtained a substrate-engaged mutant Drg1 structure, in which conserved pore-loops form a spiral staircase to interact with the polypeptide through a sequence-independent manner. Structure-based mutagenesis data highlight the functional importance of the pore-loop, the D1-D2 linker and the inter-subunit signaling motif of Drg1, which share similar regulatory mechanisms with p97. Our results suggest that Drg1 may function as an unfoldase that threads a substrate protein within the pre-60S particle.

PubMed: 36351914
DOI: 10.1038/s41467-022-34511-2

Experimental method

ELECTRON MICROSCOPY (3.6 Å)