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PMID: 17526705 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Crystal structure of the Vibrio cholerae quorum-sensing regulatory protein HapR.

Journal of bacteriology ·Vol. 189 ·No. 15 ·2007-08-00 ·Pages 5683-91

De Silva RS, Kovacikova G, Lin W, Taylor RK, Skorupski K, Kull FJ

Abstract

Quorum sensing in Vibrio cholerae involves signaling between two-component sensor protein kinases and the response regulator LuxO to control the expression of the master regulator HapR. HapR, in turn, plays a central role in regulating a number of important processes, such as virulence gene expression and biofilm formation. We have determined the crystal structure of HapR to 2.2-A resolution. Its structure reveals a dimeric, two-domain molecule with an all-helical structure that is strongly conserved with members of the TetR family of transcriptional regulators. The N-terminal DNA-binding domain contains a helix-turn-helix DNA-binding motif and alteration of certain residues in this domain completely abolishes the ability of HapR to bind to DNA, alleviating repression of both virulence gene expression and biofilm formation. The C-terminal dimerization domain contains a unique solvent accessible tunnel connected to an amphipathic cavity, which by analogy with other TetR regulators, may serve as a binding pocket for an as-yet-unidentified ligand.

MeSH Terms
Amino Acid Sequence Artificial Gene Fusion Bacterial Proteins/chemistry,genetics Crystallography, X-Ray DNA Mutational Analysis DNA, Bacterial/metabolism Dimerization Electrophoretic Mobility Shift Assay Gene Expression Genes, Reporter Helix-Turn-Helix Motifs Models, Molecular Molecular Sequence Data Mutation, Missense Protein Binding Protein Structure, Quaternary Protein Structure, Tertiary Quorum Sensing Repressor Proteins/chemistry,genetics Sequence Alignment Vibrio cholerae/chemistry,genetics beta-Galactosidase/analysis,genetics
Chemicals
Bacterial Proteins DNA, Bacterial Repressor Proteins beta-Galactosidase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
De Silva Rukman S
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
Kovacikova Gabriela
Lin Wei
Taylor Ronald K
Skorupski Karen
Kull F Jon
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/JB.01807-06
Published
2007-08-00
Epub
2007-00-25
Pages
5683-91
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC1951804
Subset
IM
Grants
NIAID NIH HHS · R01 AI072661 · United States
NIAID NIH HHS · R01 AI041558 · United States
NIAID NIH HHS · AI39654 · United States
NIAID NIH HHS · R21 AI060031 · United States
NIAID NIH HHS · R01 AI039654 · United States
NIAID NIH HHS · R01 AI072661-02 · United States
NIAID NIH HHS · AI072661 · United States
NIAID NIH HHS · AI060031 · United States
NIAID NIH HHS · R56 AI039654 · United States
NIAID NIH HHS · R29 AI041558 · United States
NIAID NIH HHS · AI41558 · United States
External Links
PubMed source DOI: 10.1128/JB.01807-06 PMC Full Text View journal details
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