2013.04.15，我院臧建业教授研究组在Journal of Biological Chemistry上发表文章:Structural basis for phosphorylated autoinducer-2 modulation of the oligomerization state of the global transcription regulator LsrR from Escherichia coli.
作者：吴旻昊、陶悦、刘晓天、臧建业
Abstract
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 signalling 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 β-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 Q33 and Y26 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. Crosslinking, 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 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.