Introduction
LuxO regulates quorum sensing. Quorum sensing is the adjustment of behavior in response to population size. As a regulator in quorum sensing pathways, LuxO can function as a “switch” and it is known to influence biofilm formation, toxin production, phosphorylation and bioluminescence. [1]
LuxO Protein Structure
Assumed Biological Structure of the signal receiver domain of the repressor protein LuxO
3cfyThe crystal structure of the whole amino acid sequence of the LuxO repressor protein is not yet available on the PDB website. The signal receiving domain of the LuxO protein in Vibrio parahaemolyticus has been successfully crystallized. However, since the paper is yet to be published, the details of the structure is not available at this time. The signal receiver domain is from residual 2 to 128. From the 3D structure, we find that this signal receiver domain consists of five and five . The phosphorylation of the aspartate at is considered to be the critical factor in the activation of LuxO regulatory protein. [2]
LuxO RNA Structure
mRNA structure of LuxO. This model is using the minimum free energy model. Different colors refer to different free energy levels.
3cfyRNA folding algorithm uses a method to minimize the free energy of the structure so that the RNA molecule is in the most stable form. [3]The red regions have higher free energy and are less stable while the blue regions posses lower energy hence more stable. Regions without base pairing are more mutable and less likely to be conserved, so evolutionarily they are more likely to contain differences. Also there are other existing models that use different algorithm to calculate the RNA secondary structure and they may give different results from the minimum free energy model.
The total free energy of this LuxO RNA folding model is -476KJ/mol.
Function
Weighted graph analysis of activation levels of various proteins in the pathogenic pathway by LuxO. Thicker lines indicate more repression in presence of LuxO deficient mutant, and therefore a higher rate of expression regulated by LuxO. Line color indicates the same information. Produced using weighted analysis platform of BioGrapher(Not yet published). The data is from the table of "Quorum-sensing regulators control virulence gene expression in Vibrio cholerae"
[1]LuxO and HapR are tow regulators as the two proteins regulate quorum sensing, related luminous marine bacterium Vibrio harveyi. LuxO and HapR control a number of other cellular processes, such as motility, protease production, and biofilm formation. Studies showed that LuxO mutant is very defective in colonization of the small intestine under an infant mouse model. By investigating the mechanism that LuxO regulated V. choleae pathogenicity, studies found that the luxO mutant does not generate any detectable TcpA or CT. Hence, the luxO mutant cannot to colonize mice. However, the LuxO effect on the virulence regulation is mediated through TcpP which express its mechanism of repression. In the evidence, luxO regulated the expression of HapR negatively. [1]
In the bacterium Vibrio harveyi, there are two quorum-sensing systems that control the bioluminescence(lux) expression. An autoinducer (AI-1 or AI-2) and a cognate sensor (LuxN or LuxQ)are contained in each system. Sensory information of the quorum-sensing systems is transmitted by a phospho-transfer mechanism to LuxO, a shared integrator protein. In term of controlling luminescence, LuxO acts negatively, which is also a member of the signal transduction proteins. LuxN and LuxQ have activities on LuxO,which is suggested by the lux phenotypes of Vibrio harveyi strains that have single and double LuxN and LuxQ mutations. [4]
Evolution
(3cfy).
Multiple sequence alignment of seven different Vibrio species. The arrows point out the places that are highly variable between different species.
3cfy
Phylogenetic Tree of LuxO gene. This is made from the MSA data from above
3cfyThe first 180 amino acids are shown in the Multiple Sequence Alignment (MSA). The MSA shows that the LuxO protein among different species of Vibrio is highly conserved except the regions highlighted by the red arrows. This is visualized by the consurf 3D model of the signal receiver domain. The dark red regions are highly conserved while the dark blue regions are highly variable. As shown in the model, the majority of the signal receiver domain of the LuxO protein are highly conserved. This is consistent with the MSA data. Study has shown that the first 104 amino acids of the LuxO is the hotspot for mutations. [2]
References
- ↑ 1.0 1.1 1.2 Zhu J, Miller MB, Vance RE, Dziejman M, Bassler BL, Mekalanos JJ. Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3129-34. Epub 2002 Feb 19. PMID:11854465 doi:10.1073/pnas.052694299
- ↑ 2.0 2.1 Dongre M, Khatri N, Dureja C, Raychaudhuri S. Alanine-scanning mutagenesis of selected residues in the N-terminal region alters the functionality of LuxO: lessons from a natural variant LuxOPL91. J Med Microbiol. 2011 Jun;60(Pt 6):856-60. Epub 2011 Feb 3. PMID:21292858 doi:10.1099/jmm.0.022988-0
- ↑ Gupta A, Rahman R, Li K, Gribskov M. Identifying complete RNA structural ensembles including pseudoknots. RNA Biol. 2012 Feb 1;9(2). PMID:22418849
- ↑ Freeman JA, Bassler BL. A genetic analysis of the function of LuxO, a two-component response regulator involved in quorum sensing in Vibrio harveyi. Mol Microbiol. 1999 Jan;31(2):665-77. PMID:10027982
