RsmA is an anti-sigma factor that modulates its activity through a [2Fe-2S] cluster cofactor.
The rsmA gene of Streptomyces coelicolor lies directly upstream of the gene encoding the group 3 sigma factor sigma(M). The RsmA protein is a putative member of the HATPase_c family of anti-sigma factors but is unusual in that it contains seven cysteine residues. Bacterial two-hybrid studies demonstrate that it interacts specifically with sigma(M), and in vitro studies of the purified proteins by native PAGE and transcription assays confirmed that they form a complex. Characterization of RsmA revealed that it binds ATP and that, as isolated, it contains significant quantities of iron and inorganic sulfide, in equal proportion, with spectroscopic properties characteristic of a [2Fe-2S] cluster-containing protein. Importantly, the interaction between RsmA and sigma(M) is dependent on the presence of the iron-sulfur cluster. We propose a model in which RsmA regulates the activity of sigma(M). Loss of the cluster, in response to an as yet unidentified signal, activates sigma(M) by abolishing its interaction with the anti-sigma factor. This represents a major extension of the functional diversity of iron-sulfur cluster proteins.
Gaskell
Alisa A
AA
Centre for Metalloprotein Spectroscopy and Biology, School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
Crack
Jason C
JC
Kelemen
Gabriella H
GH
Hutchings
Matthew I
MI
Le Brun
Nick E
NE
D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D007506:Iron-Sulfur Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010957:Plasmids; D017386:Sequence Homology, Amino Acid; D012808:Sigma Factor / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D048372:Streptomyces coelicolor / Q000235:genetics; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000032:analysis
D001426:Bacterial Proteins; D007506:Iron-Sulfur Proteins; D012808:Sigma Factor; D000255:Adenosine Triphosphate; D001616:beta-Galactosidase; D003545:Cysteine