## 5 Mechanisms for Triggering \(\sigma\) Factor Release from Anti-\(\sigma\) Factors
### Partner-Switching  
Partner-switching mechanisms are widespread, particularly among Gram-positive bacteria, and have been extensively studied for the Group 3 sigma factors \(\sigma^{\mathrm{B}}\) and \(\sigma^{\mathrm{F}}\) in _B. subtilis_. Although these \(\sigma\) factors use different sensing mechanisms to modulate their district biological activities, the fundamental components that control \(\sigma\) activity are homologous. There are four basic components (named for the \(\sigma^{\mathrm{B}}\) system): \(\sigma\) factor (\(\sigma^{\mathrm{B}}\)); anti-\(\sigma\) factor/protein kinase (RsbW); anti-anti-\(\sigma\) factor (RsbV); and input phosphatase complex (RsbTU or RsbQP) (Figure 4c). In unstressed cells \(\sigma^{\mathrm{B}}\) is held inactive by RsbW; RsbW can alternatively bind to the non-phosphorylated form of RsbV, but RsbW itself antagonizes this interaction by phosphorylating RsbV to RsbV-P (Figure 4c). The phosphorylation status of RsbV is therefore crucial to the active state of \(\sigma^{\mathrm{B}}\). To activate the general stress response, RsbTU or RsbQP dephosphorylate RsbV, thereby allowing RsbV to bind RsbW and liberate \(\sigma^{\mathrm{B}}\). RsbTU and RsbQP are alternative phosphatases consisting of a phosphatase component (RsbU/RsbP) and a cognate activator (RsbT/RsbQ), that allow the integration of environmental and energy stress, respectively. Environmental stresses such as heat lead to the activation of RsbU phosphatase via a complex pathway that involves at least 10 proteins including a 1.8 MDa cytoplasmic protein complex known as the stressorsome, which is the source of RsbT [46, 88]. The activity of the RsbP phosphatase is thought to be modulated by the direct sensing of an unknown energy-related metabolite that is possibly provided by its partner hydrolase protein, RsbQ [89].  
In \(\alpha\)-proteobacteria, including epiphytes _Methylobacterium extorquens_ and _Sphingomonas melonis_, and _Caulobacter crescentus_, an unusual partner-switching mechanism involving three often genetically-linked gene products exists to control the general stress response. Using the _M. extorquens_ nomenclature, the key players are \(\sigma^{\mathrm{EcrfG1}}\), its anti-\(\sigma\) factor NepR and PhyR. PhyR was originally identified as an activator of stress-related genes associated with growth in the harsh environment of the leaf surface and unusually consists of an N-terminal ECF \(\sigma\)-like domain and a C-terminal response regulator receiver domain [90]. However, rather than acting as a \(\sigma\), PhyR is a \(\sigma\) factor mimic, regulating transcription indirectly by binding to NepR when the receiver domain is phosphorylated, thereby freeing \(\sigma^{\text{EcfG1}}\)[91]. The \(\sigma\)-like domain of PhyR (PhyRsl) consists of \(\sigma\)- and \(\sigma\)-like subdomains and is occluded by the receiver domain in the unphosphorylated form [92]. This regulatory arrangement allows multiple stress signals to converge on PhyR, leading to the activation of \(\sigma^{\text{EcfG1}}\) and this is the case in _S. melonis_ where seven histidine kinases were recently implicated in the phosphorylation of PhyR in response to distinct stress signals [93].