An acetylatable lysine controls CRP function in E. coli

Robert Davis, Ana Écija-Conesa, Julia Gallego-Jara, Teresa de Diego, Ekaterina V. Filippova, Gina Kuffel, Wayne F. Anderson, Bradford W. Gibson, Birgit Schilling, Manuel Canovas*, Alan J. Wolfe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Transcriptional regulation is the key to ensuring that proteins are expressed at the proper time and the proper amount. In Escherichia coli, the transcription factor cAMP receptor protein (CRP) is responsible for much of this regulation. Questions remain, however, regarding the regulation of CRP activity itself. Here, we demonstrate that a lysine (K100) on the surface of CRP has a dual function: to promote CRP activity at Class II promoters, and to ensure proper CRP steady state levels. Both functions require the lysine's positive charge; intriguingly, the positive charge of K100 can be neutralized by acetylation using the central metabolite acetyl phosphate as the acetyl donor. We propose that CRP K100 acetylation could be a mechanism by which the cell downwardly tunes CRP-dependent Class II promoter activity, whilst elevating CRP steady state levels, thus indirectly increasing Class I promoter activity. This mechanism would operate under conditions that favor acetate fermentation, such as during growth on glucose as the sole carbon source or when carbon flux exceeds the capacity of the central metabolic pathways.

Original languageEnglish (US)
Pages (from-to)116-131
Number of pages16
JournalMolecular Microbiology
Volume107
Issue number1
DOIs
StatePublished - Jan 2018

Funding

We acknowledge María José López Andreo for her interest and technical assistance and Stephen Busby and Douglas Browning for their thoughts and suggestions. We also would like to thank Stephen Busby for his generous gift of pRW50 CC(-61.5). This work was supported by grants from the U.S. Department of Energy (DOE) (DE-SC00124430 to AJW, BG and BS), the Ministry of Science and Innovation (BIO2014– 54411-C2-1-R to MC) (which includes ERDF European co-funding) and the Seneca Foundation CARM (19236/PI/14 to MC). This work also was supported by an National Center for Research Resources (NCRR) shared instrumentation grant for the TripleTOF 6600 (1S10 OD016281, BWG). The authors have no competing interests.

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

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