A Structural Code for Assembly Specificity in GID/CTLH-Type E3 Ligases
van gen Hassend, P. M.; Schindelin, H.
Show abstract
GID/CTLH-type E3 ligases assemble into conserved ring-shaped architectures built from repeating LisH-CTLH-CRA modules, yet the molecular rules that enforce their highly specific subunit arrangement have remained unknown. Here, we decode the structural "assembly specificity code" that governs CRA-CRA pairing. Using crystal structures of multiple CTLH-CRA domains, including the RanBP9-muskelin heterodimer, integrated with quantitative binding analyses, we show that several interfaces operate with exceptionally high affinity, reaching the picomolar range, and that conserved sequence and geometric features enable each subunit to only select cognate partners. Strikingly, targeted perturbations of these features are sufficient to reprogram pairing preferences, enabling engineered subunits such as RanBP10 or Twa1 to adopt non-native interaction partners. These findings reveal the molecular logic that preserves the architecture of GID/CTLH-type E3 ligases and demonstrate that their assembly code is both decipherable and engineerable, providing a conceptual foundation for reconfiguring these ring-shaped E3 ligases.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Structure of the teneurin-latrophilin complex: Alternative splicing controls synapse specificity by a novel mechanism 96%
- BRCA2 stabilises RAD51 and DMC1 nucleoprotein filaments through a conserved interaction mode 96%
- Structural insights into p300 regulation and acetylation-dependent genome organisation 96%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Unique structural features govern the activity of a human mitochondrial AAA+ disaggregase, Skd3. 97%
- Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone 96%
- Structural basis for competitive binding of productive and degradative co-transcriptional effectors to the nuclear cap-binding complex 96%
Similar papers in this journal
"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.