Tomoki Himiyama, Yuko Tsuchiya, Yasushige Yonezawa, Tsutomu Nakamura
Bioconjugate chemistry 2021 Jan 20Direct 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.
Tomoki Himiyama, Yuko Tsuchiya, Yasushige Yonezawa, Tsutomu Nakamura. Rebuilding Ring-Type Assembly of Peroxiredoxin by Chemical Modification. Bioconjugate chemistry. 2021 Jan 20;32(1):153-160
PMID: 33334100
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