Rebuilding Ring-Type Assembly of Peroxiredoxin by Chemical Modification

Bioconjug Chem. 2021 Jan 20;32(1):153-160. doi: 10.1021/acs.bioconjchem.0c00587. Epub 2020 Dec 17.


Direct control of the protein quaternary structure (QS) is challenging owing to the complexity of the protein structure. As a protein with a characteristic QS, peroxiredoxin from Aeropyrum pernix K1 (ApPrx) forms a decamer, wherein five dimers associate to form a ring. Here, we disrupted and reconstituted ApPrx QS via amino acid mutations and chemical modifications targeting hot spots for protein assembly. The decameric QS of an ApPrx* mutant, wherein all cysteine residues in wild-type ApPrx were mutated to serine, was destructed to dimers via an F80C mutation. The dimeric ApPrx*F80C mutant was then modified with a small molecule and successfully assembled as a decamer. Structural analysis confirmed that an artificially installed chemical moiety potentially facilitates suitable protein-protein interactions to rebuild a native structure. Rebuilding of dodecamer was also achieved through an additional amino acid mutation. This study describes a facile method to regulate the protein assembly state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Cyclization
  • Peroxiredoxins / chemistry*
  • Peroxiredoxins / metabolism
  • Protein Conformation


  • Peroxiredoxins