RsmA is an anti-sigma factor that modulates its activity through a [2Fe-2S] cluster cofactor

Abstract

The rsmA gene of Streptomyces coelicolor lies directly upstream of the gene encoding the group 3 sigma factor σM. 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 σM, 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 σM is dependent on the presence of the iron-sulfur cluster. We propose a model in which RsmA regulates the activity of σM. Loss of the cluster, in response to an as yet unidentified signal, activates σM by abolishing its interaction with the anti-sigma factor. This represents a major extension of the functional diversity of iron-sulfur cluster proteins. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.