Lysine pyrrolation is a naturally-occurring covalent modification involved in the production of DNA mimic proteins

Hiroaki Miyashita, Miho Chikazawa, Natsuki Otaki, Yusuke Hioki, Yuki Shimozu, Fumie Nakashima, Takahiro Shibata, Yoshihisa Hagihara, Shoichi Maruyama, Noriyoshi Matsumi, Koji Uchida

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Covalent modification of proteins exerts significant effects on their chemical properties and has important functional and regulatory consequences. We now report the identification and verification of an electrically-active form of modified proteins recognized by a group of small molecules commonly used to interact with DNA. This previously unreported property of proteins was initially discovered when the Î 3-ketoaldehydes were identified as a source of the proteins stained by the DNA intercalators. Using 1,4-butanedial, the simplest Î 3-ketoaldehyde, we characterized the structural and chemical criteria governing the recognition of the modified proteins by the DNA intercalators and identified N Îμ-pyrrolelysine as a key adduct. Unexpectedly, the pyrrolation conferred an electronegativity and electronic properties on the proteins that potentially constitute an electrical mimic to the DNA. In addition, we found that the pyrrolated proteins indeed triggered an autoimmune response and that the production of specific antibodies against the pyrrolated proteins was accelerated in human systemic lupus erythematosus. These findings and the apparent high abundance of N Îμ-pyrrolelysine in vivo suggest that protein pyrrolation could be an endogenous source of DNA mimic proteins, providing a possible link connecting protein turnover and immune disorders.

Original languageEnglish
Article number5343
JournalScientific reports
Volume4
DOIs
Publication statusPublished - Jun 18 2014
Externally publishedYes

ASJC Scopus subject areas

  • General

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