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Structure of GrlR–GrlA complex that prevents GrlA activation of virulence genes

Author

Listed:
  • Abhilash Padavannil

    (National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore)

  • Chacko Jobichen

    (National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore)

  • Erez Mills

    (Faculty of Medicine, IMRIC, The Hebrew University)

  • Adrian Velazquez-Campoy

    (Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint-Unit IQFR-CSIC-BIFI
    University of Zaragoza
    Fundacion ARAID, Government of Aragon)

  • Mo Li

    (National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore)

  • Ka Yin Leung

    (Trinity Western University, 7600 Glover Road, Langley, British Columbia, Canada V2Y 1Y1
    State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology)

  • Yu Keung Mok

    (National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore)

  • Ilan Rosenshine

    (Faculty of Medicine, IMRIC, The Hebrew University)

  • J. Sivaraman

    (National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore)

Abstract

The locus of enterocyte effacement (LEE) is essential for virulence of enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). The 41 genes of the LEE encode type III secretion system proteins and three associated regulators: Ler, GrlA and GrlR. Ler is a positive regulator for most of the LEE operons, including grlRA. GrlA controls the expression of ler, ehxCABD and flhDC operons. GrlR binds to GrlA and suppresses its function. Here we report the crystal structure of GrlR–GrlAΔ (aa 1–106) complex (2:1) and its functional characterization. We show that GrlR interacts with the Helix-Turn-Helix motif of GrlA. Moreover, GrlA binds to the promoter DNA fragments of ler, ehxCABD and flhDC, and GrlR outcompetes with these promoter DNA sequences for the Helix-Turn-Helix motif of GrlA. These findings provide mechanistic insight into a regulatory module for the virulence of EPEC and EHEC, two important pathogens that cause devastating diseases.

Suggested Citation

  • Abhilash Padavannil & Chacko Jobichen & Erez Mills & Adrian Velazquez-Campoy & Mo Li & Ka Yin Leung & Yu Keung Mok & Ilan Rosenshine & J. Sivaraman, 2013. "Structure of GrlR–GrlA complex that prevents GrlA activation of virulence genes," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3546
    DOI: 10.1038/ncomms3546
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