Crystal structure of the Escherichia coli regulator of σ70, Rsd, in complex with σ70 domain 4

The Escherichia coli Rsd protein binds tightly and specifically to the RNA polymerase (RNAP) sigma(70) factor. Rsd plays a role in alternative a factor-dependent transcription by biasing the competition between (570 and alternative or factors for the available core RNAP. Here, we determined the 2.6 angstrom-resolution X-ray crystal structure of Rsd bound to 70 domain 4 (sigma(70)(4)), the primary determinant for Rsd binding within sigma(70). The structure reveals that Rsd binding interferes with the two primary functions of 0704, core RNAP binding and promoter -35 element binding. Interestingly, the most highly conserved Rsd residues form a network of interactions through the middle of the Rsd structure that connect the sigma(70)(4)-binding surface with three cavities exposed on distant surfaces of Rsd, suggesting functional coupling between sigma(70)(4) binding and other binding surfaces of Rsd, either for other proteins or for as yet unknown small molecule effectors. These results provide a structural basis for understanding the role of Rsd, as well as its ortholog, AlgQ, a positive regulator of Psendonionas aeruginosa virulence, in transcription regulation.