The significance of EXDD and RXKD motif conservation in Rel proteins

Mathew Sajish, Sissy Kalayil, Sunil Kumar Verma, Vinay Kumar Nandicoori, Balaji Prakash

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Monofunctional and bifunctional classes of Rel proteins catalyze pyrophosphoryl transfer from ATP to 3′-OH of GTP/GDP to synthesize (p)ppGpp, which is essential for normal microbial physiology and survival. Bifunctional proteins additionally catalyze the hydrolysis of (p)ppGpp.Wehave earlier demonstrated that although both catalyze identical the (p)ppGpp synthesis reaction, they exhibit a differential response to Mg2+ due to a unique charge reversal in the synthesis domain; an RXKD motif in the synthesis domain of bifunctional protein is substituted by an EXDDmotif in that of the monofunctional proteins. Here, we show that these motifs also determine substrate specificities (GTP/GDP), cooperativity, and regulation of catalytic activities at the N-terminal region through the C-terminal region. Most importantly, a mutant bifunctional Rel carrying an EXDD instigates a novel catalytic reaction, resulting in the synthesis of pGpp by an independent hydrolysis of the 5′Pα-O-Pβ bond of GTP/GDP or (p)ppGpp. Further experiments with RelA from Escherichia coli wherein EXDD is naturally present also revealed the presence of pGpp, albeit at low levels. This work brings out the biological significance of RXKD/ EXDDmotif conservation in Rel proteins and reveals an additional catalytic activity for the monofunctional proteins, prompting an extensive investigation for the possible existence and role of pGpp in the biological system.

Original languageEnglish (US)
Pages (from-to)9115-9123
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number14
DOIs
StatePublished - Apr 3 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Sajish, M., Kalayil, S., Verma, S. K., Nandicoori, V. K., & Prakash, B. (2009). The significance of EXDD and RXKD motif conservation in Rel proteins. Journal of Biological Chemistry, 284(14), 9115-9123. https://doi.org/10.1074/jbc.M807187200