Structural highlights
Function
[LSRR_ECOLI] Regulates transcription of many different genes. In the absence of autoinducer 2 (AI-2), represses transcription of the lsrACDBFG operon and its own transcription. In the presence of AI-2, LsrR is inactivated by binding phospho-AI-2, leading to the transcription of the lsr genes.[1] [2] [3]
Publication Abstract from PubMed
Quorum-sensing systems are widely used by bacteria to control behavior in response to fluctuations in cell density. Several small diffusible molecules called autoinducers act as signaling molecules in quorum-sensing processes through interplay with sensors. Autoinducers modulate vital physiological functions such as nutrient acquisition, gene transcription, and virulence factor production. In Escherichia coli, LsrR serves as a global transcription regulator that responds to autoinducer-2 to regulate the expression of a variety of genes, including the lsr operon and the lsrR gene. Here, we report the crystal structure of full-length LsrR from E. coli, which has an N-terminal DNA-binding domain and a C-terminal ligand-binding domain connected by a beta-strand. Although only two molecules are found in one asymmetric unit, two neighboring dimers pack to form a tetramer that is consistent with the oligomerization state of LsrR in solution. Mutagenesis experiments and gel shift assays indicated that Gln-33 and Tyr-26 might be involved in interactions between LsrR and DNA. The LsrR-binding site for phosphorylated autoinducer-2 was predicted by structural comparisons of LsrR with CggR and SorC. Cross-linking, size exclusion chromatography, and gel shift assays determined that phosphorylated autoinducer-2 triggered the disassembly of the LsrR tetramer into dimers and reduced the DNA binding ability of LsrR. Our findings reveal a mechanism for the change in the oligomerization state of LsrR in the presence of phosphorylated autoinducer-2. Based on these observations, we propose that phosphorylated autoinducer-2 triggers the disassembly of the LsrR tetramer to activate the transcription of its target genes.
Structural Basis for Phosphorylated Autoinducer-2 Modulation of the Oligomerization State of the Global Transcription Regulator LsrR from Escherichia coli.,Wu M, Tao Y, Liu X, Zang J J Biol Chem. 2013 May 31;288(22):15878-87. doi: 10.1074/jbc.M112.417634. Epub, 2013 Apr 15. PMID:23589368[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xavier KB, Bassler BL. Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli. J Bacteriol. 2005 Jan;187(1):238-48. PMID:15601708 doi:http://dx.doi.org/187/1/238
- ↑ Wang L, Hashimoto Y, Tsao CY, Valdes JJ, Bentley WE. Cyclic AMP (cAMP) and cAMP receptor protein influence both synthesis and uptake of extracellular autoinducer 2 in Escherichia coli. J Bacteriol. 2005 Mar;187(6):2066-76. PMID:15743955 doi:http://dx.doi.org/187/6/2066
- ↑ Li J, Attila C, Wang L, Wood TK, Valdes JJ, Bentley WE. Quorum sensing in Escherichia coli is signaled by AI-2/LsrR: effects on small RNA and biofilm architecture. J Bacteriol. 2007 Aug;189(16):6011-20. Epub 2007 Jun 8. PMID:17557827 doi:http://dx.doi.org/JB.00014-07
- ↑ Wu M, Tao Y, Liu X, Zang J. Structural Basis for Phosphorylated Autoinducer-2 Modulation of the Oligomerization State of the Global Transcription Regulator LsrR from Escherichia coli. J Biol Chem. 2013 May 31;288(22):15878-87. doi: 10.1074/jbc.M112.417634. Epub, 2013 Apr 15. PMID:23589368 doi:10.1074/jbc.M112.417634
