Structure of an atypical orphan response regulator protein supports a new phosphorylation-independent regulatory mechanism

Eunmi Hong, Mi Lee Hyang, Hyunsook Ko, Dong Uk Kim, Byoung Young Jeon, Jinwon Jung, Joon Shin, Sung Ah Lee, Yangmee Kim, Ho Jeon Young, Chaejoon Cheong, Hyun Soo Cho, Weontae Lee

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Abstract

Two-component signal transduction systems, commonly found in prokaryotes, typically regulate cellular functions in response to environmental conditions through a phosphorylation-dependent process. A new type of response regulator, hp1043 (HP-RR) from Helicobacter pylori, has been recently identified. HP-RR is essential for cell growth and does not require the well known phosphorelay scheme. Unphosphorylated HP-RR binds specifically to its own promoter (P 1043) and autoregulates the promoter of the tlpB gene (P tlpB). We have determined the structure of HP-RR by NMR and x-ray crystallography, revealing a symmetrical dimer with two functional domains. The molecular topology resembles that of the OmpR/PhoB subfamily, however, the symmetrical dimer is stable even in the unphosphorylated state. The dimer interface, formed by three secondary structure elements (α4-β5- α5), resembles that of the active, phosphorylated forms of ArcA and PhoB. Several conserved residues of the HP-RR dimeric interface deviate from the OmpR/PhoB subfamily, although there are similar salt bridges and hydrophobic patches within the interface. Our findings reveal how a new type of response regulator protein could function as a cell growth-associated regulator in the absence of post-translational modification.

Original languageEnglish
Pages (from-to)20667-20675
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number28
DOIs
Publication statusPublished - 2007 Jul 13

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hong, E., Hyang, M. L., Ko, H., Kim, D. U., Jeon, B. Y., Jung, J., Shin, J., Lee, S. A., Kim, Y., Young, H. J., Cheong, C., Cho, H. S., & Lee, W. (2007). Structure of an atypical orphan response regulator protein supports a new phosphorylation-independent regulatory mechanism. Journal of Biological Chemistry, 282(28), 20667-20675. https://doi.org/10.1074/jbc.M609104200