Insight into the RssB-Mediated Recognition and Delivery of σ to the AAA+ Protease, ClpXP.

In , SigmaS (σ) is the master regulator of the general stress response. The cellular levels of σ are controlled by transcription, translation and protein stability. The turnover of σ, by the AAA+ protease (ClpXP), is tightly regulated by a dedicated adaptor protein, termed RssB (Regulator of Sigma S protein B)-which is an atypical member of the response regulator (RR) family.

Molecular and structural insights into an asymmetric proteolytic complex (ClpP1P2) from Mycobacterium smegmatis.

The ClpP protease is found in all kingdoms of life, from bacteria to humans. In general, this protease forms a homo-oligomeric complex composed of 14 identical subunits, which associates with its cognate ATPase in a symmetrical manner. Here we show that, in contrast to this general architecture, the Clp protease from Mycobacterium smegmatis (Msm) forms an asymmetric hetero-oligomeric complex ClpP1P2, which only associates with its cognate ATPase through the ClpP2 ring.

Anti-adaptors use distinct modes of binding to inhibit the RssB-dependent turnover of RpoS (σ(S)) by ClpXP.

In Escherichia coli, σ(S) is the master regulator of the general stress response. The level of σ(S) changes in response to multiple stress conditions and it is regulated at many levels including protein turnover. In the absence of stress, σ(S) is rapidly degraded by the AAA+ protease, ClpXP in a regulated manner that depends on the adaptor protein RssB.