Structural insights into the regulation of Bacillus subtilis SigW activity by anti-sigma RsiW.
Bacillus subtilis SigW is localized to the cell membrane and is inactivated by the tight interaction with anti-sigma RsiW under normal growth conditions. Whereas SigW is discharged from RsiW binding and thus initiates the transcription of its regulon under diverse stress conditions such as antibiotics and alkaline shock. The release and activation of SigW in response to extracytoplasmic signals is induced by the regulated intramembrane proteolysis of RsiW. As a ZAS (Zinc-containing anti-sigma) family protein, RsiW has a CHCC zinc binding motif, which implies that its anti-sigma activity may be regulated by the state of zinc coordination in addition to the proteolytic cleavage of RsiW. To understand the regulation mode of SigW activity by RsiW, we determined the crystal structures of SigW in complex with the cytoplasmic domain of RsiW, and compared the conformation of the CHCC motif in the reduced/zinc binding and the oxidized states. The structures revealed that RsiW inhibits the promoter binding of SigW by interacting with the surface groove of SigW. The interaction between SigW and RsiW is not disrupted by the oxidation of the CHCC motif in RsiW, suggesting that SigW activity might not be regulated by the zinc coordination states of the CHCC motif.
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, South Korea.
Shankar Raj
SR
Devkota
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, South Korea.
Eunju
E
Kwon
Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea.
Sung Chul
SC
Ha
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, South Korea.
Hyeun Wook
HW
Chang
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, South Korea.
Dong Young
http://orcid.org/0000-0001-7594-9083
DY
Kim
D000595:Amino Acid Sequence; D001412:Bacillus subtilis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002850:Chromatography, Gel; D004926:Escherichia coli; D007834:Lasers; D008027:Light; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000072417:Protein Domains; D011994:Recombinant Proteins / Q000378:metabolism; D012542:Scattering, Radiation; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D001426:Bacterial Proteins; D011994:Recombinant Proteins; C413458:SigW protein, Bacillus subtilis; D012808:Sigma Factor; D015032:Zinc