Crystal structure of SmcR, a quorum-sensing master regulator of Vibrio vulnificus, provides insight into its regulation of transcription.
Quorum sensing has been implicated as an important global regulatory system controlling the expression of numerous virulence factors in bacterial pathogens. SmcR, a homologue of Vibrio harveyi LuxR, has been proposed as a quorum-sensing master regulator of Vibrio vulnificus, an opportunistic human pathogen. Previous studies demonstrated that SmcR is essential for the survival and pathogenesis of V. vulnificus, indicating that inhibiting SmcR is an attractive approach to combat infections by the bacteria. Here, we determined the crystal structure of SmcR at 2.1 A resolution. The protein structure reveals a typical TetR superfamily fold consisting of an N-terminal DNA binding domain and a C-terminal dimerization domain. In vivo and in vitro functional analysis of the dimerization domain suggested that dimerization of SmcR is vital for its biological regulatory function. The N-terminal DNA recognition and binding residues were assigned based on the protein structure and the results of in vivo and in vitro mutagenesis experiments. Furthermore, protein-DNA interaction experiments suggested that SmcR may have a sophisticated mechanism that enables the protein to recognize each of its many target operators with different affinities.
Kim
Yoonjeong
Y
Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806.
Kim
Byoung Sik
BS
Park
Yu Jin
YJ
Choi
Won-Chan
WC
Hwang
Jungwon
J
Kang
Beom Sik
BS
Oh
Tae-Kwang
TK
Choi
Sang Ho
SH
Kim
Myung Hee
MH
D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D016296:Mutagenesis; D017510:Protein Folding; D055503:Protein Multimerization / Q000502:physiology*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D053038:Quorum Sensing / Q000502:physiology; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D041261:Vibrio vulnificus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity
D001426:Bacterial Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C410093:smcR protein, Vibrio vulnificus; C064778:LuxR autoinducer binding proteins