| Structural highlights
Function
FLEQ_PSEAE AAA+ ATPase enhancer-binding protein that acts as a transcription regulator and plays a role in the modulation of mucin adhesion and flagellar gene expression (PubMed:9287015, PubMed:11673434, PubMed:26362077). In addition to flagella genes, regulates also expression of biofilm-related genes (PubMed:22581773). Functions as a transcriptional repressor in the absence of c-di-GMP and as an activator when c-di-GMP is present (PubMed:22581773).[1] [2] [3] [4]
Publication Abstract from PubMed
FleQ is an AAA+ ATPase enhancer-binding protein that regulates both flagella and biofilm formation in the opportunistic pathogen Pseudomonas aeruginosa. FleQ belongs to the NtrC subfamily of response regulators, but lacks the corresponding aspartic acid for phosphorylation in the REC domain (FleQ(R), also named FleQ domain). Here, we show that the atypical REC domain of FleQ is essential for the function of FleQ. Crystal structure of FleQ(R) at 2.3A reveals that the structure of FleQ(R) is significantly different from the REC domain of NtrC1 which regulates gene expression in a phosphorylation dependent manner. FleQ(R) forms a novel active dimer (transverse dimer), and mediates the dimerization of full-length FleQ in an unusual manner. Point mutations that affect the dimerization of FleQ lead to loss of function of the protein. Moreover, a c-di-GMP binding site deviating from the previous reported one is identified through structure analysis and point mutations.
The REC domain mediated dimerization is critical for FleQ from Pseudomonas aeruginosa to function as a c-di-GMP receptor and flagella gene regulator.,Su T, Liu S, Wang K, Chi K, Zhu D, Wei T, Huang Y, Guo L, Hu W, Xu S, Lin Z, Gu L J Struct Biol. 2015 Oct;192(1):1-13. doi: 10.1016/j.jsb.2015.09.002. Epub 2015, Sep 8. PMID:26362077[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dasgupta N, Ramphal R. Interaction of the antiactivator FleN with the transcriptional activator FleQ regulates flagellar number in Pseudomonas aeruginosa. J Bacteriol. 2001 Nov;183(22):6636-44. PMID:11673434 doi:10.1128/JB.183.22.6636-6644.2001
- ↑ Baraquet C, Murakami K, Parsek MR, Harwood CS. The FleQ protein from Pseudomonas aeruginosa functions as both a repressor and an activator to control gene expression from the pel operon promoter in response to c-di-GMP. Nucleic Acids Res. 2012 Aug;40(15):7207-18. PMID:22581773 doi:10.1093/nar/gks384
- ↑ Su T, Liu S, Wang K, Chi K, Zhu D, Wei T, Huang Y, Guo L, Hu W, Xu S, Lin Z, Gu L. The REC domain mediated dimerization is critical for FleQ from Pseudomonas aeruginosa to function as a c-di-GMP receptor and flagella gene regulator. J Struct Biol. 2015 Oct;192(1):1-13. doi: 10.1016/j.jsb.2015.09.002. Epub 2015, Sep 8. PMID:26362077 doi:http://dx.doi.org/10.1016/j.jsb.2015.09.002
- ↑ Arora SK, Ritchings BW, Almira EC, Lory S, Ramphal R. A transcriptional activator, FleQ, regulates mucin adhesion and flagellar gene expression in Pseudomonas aeruginosa in a cascade manner. J Bacteriol. 1997 Sep;179(17):5574-81. PMID:9287015 doi:10.1128/jb.179.17.5574-5581.1997
- ↑ Su T, Liu S, Wang K, Chi K, Zhu D, Wei T, Huang Y, Guo L, Hu W, Xu S, Lin Z, Gu L. The REC domain mediated dimerization is critical for FleQ from Pseudomonas aeruginosa to function as a c-di-GMP receptor and flagella gene regulator. J Struct Biol. 2015 Oct;192(1):1-13. doi: 10.1016/j.jsb.2015.09.002. Epub 2015, Sep 8. PMID:26362077 doi:http://dx.doi.org/10.1016/j.jsb.2015.09.002
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