Back

Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome

Draczkowski, P.; Chen, S.-N.; Chen, T.; Wang, Y.-S.; Huang, J. Y. C.; Tsai, M.-C.; Lin, S.-Y.; Viner, R.; Chang, Y.-C.; Wu, K.-P.; Hsu, S.-T. D.

2025-01-13 biochemistry
10.1101/2025.01.13.632666 bioRxiv
Show abstract

Beyond the canonical K48-linked homotypic polyubiquitination for proteasome-targeted proteolysis, K11/K48-branched ubiquitin (Ub) chains are involved in fast-tracking protein turnover during cell cycle progression and proteotoxic stress. Here, we report cryo-EM structures of human 26S proteasome in a complex with a K11/K48-branched Ub chain. The structures revealed a multivalent substrate recognition mechanism involving a hitherto unknown K11-linked Ub binding site at the groove formed by RPN2 and RPN10 in addition to the canonical K48-linkage binding site formed by RPN10 and RPT4/5 coiled-coil. Additionally, RPN2 recognizes an alternating K11-K48 linkage through a conserved motif similar to the K48-specific T1 binding site of RPN1. The insights gleaned from these structures explain the molecular mechanism underlying the recognition of the K11/K48 branched Ub as a priority signal in the ubiquitin-mediated proteasomal degradation.

Published in Nature Communications (predicted rank #1) · training set

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.