Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase

Fangliang Zhang, Devang M. Patel, Kristen Colavita, Irina Rodionova, Brian Buckley, David A. Scott, Akhilesh Kumar, Svetlana A. Shabalina, Sougata Saha, Mikhail Chernov, Andrei L. Osterman, Anna Kashina

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Protein arginylation is an emerging post-translational modification that targets a number of metabolic enzymes; however, the mechanisms and downstream effects of this modification are unknown. Here we show that lack of arginylation renders cells vulnerable to purine nucleotide synthesis inhibitors and affects the related glycine and serine biosynthesis pathways. We show that the purine nucleotide biosynthesis enzyme PRPS2 is selectively arginylated, unlike its close homologue PRPS1, and that arginylation of PRPS2 directly facilitates its biological activity. Moreover, selective arginylation of PRPS2 but not PRPS1 is regulated through a coding sequence-dependent mechanism that combines elements of mRNA secondary structure with lysine residues encoded near the N-terminus of PRPS1. This mechanism promotes arginylation-specific degradation of PRPS1 and selective retention of arginylated PRPS2 in vivo. We therefore demonstrate that arginylation affects both the activity and stability of a major metabolic enzyme.

Original languageEnglish (US)
Article number7517
JournalNature communications
Volume6
DOIs
StatePublished - Jul 15 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase'. Together they form a unique fingerprint.

  • Cite this

    Zhang, F., Patel, D. M., Colavita, K., Rodionova, I., Buckley, B., Scott, D. A., Kumar, A., Shabalina, S. A., Saha, S., Chernov, M., Osterman, A. L., & Kashina, A. (2015). Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophosphate synthase. Nature communications, 6, [7517]. https://doi.org/10.1038/ncomms8517