Structure of an atypical orphan response regulator protein supports a new phosphorylation-independent regulatory mechanism.
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 (alpha4-beta5-alpha5), 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.
Hong
Eunmi
E
Department of Biochemistry and HTSD-NMR & Application NRL, College of Science, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul 120-749, Korea.
Lee
Hyang Mi
HM
Ko
Hyunsook
H
Kim
Dong-Uk
DU
Jeon
Byoung-Young
BY
Jung
Jinwon
J
Shin
Joon
J
Lee
Sung-Ah
SA
Kim
Yangmee
Y
Jeon
Young Ho
YH
Cheong
Chaejoon
C
Cho
Hyun-Soo
HS
Lee
Weontae
W
D018360:Crystallography, X-Ray; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D016480:Helicobacter pylori / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D004269:DNA, Bacterial; C501059:HP1043 protein, Helicobacter pylori; D014157:Transcription Factors