The MIDAS domain of AAA mechanoenzyme Mdn1 forms catch bonds with two different substrates

Elife. 2022 Feb 11;11:e73534. doi: 10.7554/eLife.73534.


Catch bonds are a form of mechanoregulation wherein protein-ligand interactions are strengthened by the application of dissociative tension. Currently, the best-characterized examples of catch bonds are between single protein-ligand pairs. The essential AAA (ATPase associated with diverse cellular activities) mechanoenzyme Mdn1 drives at least two separate steps in ribosome biogenesis, using its MIDAS domain to extract the ubiquitin-like (UBL) domain-containing proteins Rsa4 and Ytm1 from ribosomal precursors. However, it must subsequently release these assembly factors to reinitiate the enzymatic cycle. The mechanism underlying the switching of the MIDAS-UBL interaction between strongly and weakly bound states is unknown. Here, we use optical tweezers to investigate the force dependence of MIDAS-UBL binding. Parallel experiments with Rsa4 and Ytm1 show that forces up to ~4 pN, matching the magnitude of force produced by AAA proteins similar to Mdn1, enhance the MIDAS domain binding lifetime up to 10-fold, and higher forces accelerate dissociation. Together, our studies indicate that Mdn1's MIDAS domain can form catch bonds with more than one UBL substrate, and provide insights into how mechanoregulation may contribute to the Mdn1 enzymatic cycle during ribosome biogenesis.

Keywords: catch bond; molecular biophysics; none; optical tweezers; ribosome biogenesis; structural biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Binding Sites
  • Ligands
  • Optical Tweezers
  • Organelle Biogenesis
  • Protein Binding
  • Protein Domains
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • Ribosomes / physiology*
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Single Molecule Imaging
  • Ubiquitin / genetics*


  • Ligands
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • Ubiquitin
  • MDN1 protein, S cerevisiae
  • Mdn1 protein, S pombe
  • ATPases Associated with Diverse Cellular Activities