Roles of adaptor proteins in regulation of bacterial proteolysis

Abstract

Elimination of non-functional or unwanted proteins is critical for cell growth and regulation. In bacteria, ATP-dependent proteases target cytoplasmic proteins for degradation, contributing to both protein quality control and regulation of specific proteins, thus playing roles parallel to that of the proteasome in eukaryotic cells. Adaptor proteins provide a way to modulate the substrate specificity of the proteases and allow regulated proteolysis. Advances over the past few years have provided new insight into how adaptor proteins interact with both substrates and proteases and how adaptor functions are regulated. An important advance has come with the recognition of the critical roles of anti-adaptor proteins in regulating adaptor availability.

Figure 1. Regulation of RpoS proteolysis in E. coli and Salmonella

RpoS (σ^S) is degraded by the ClpXP protease via its interaction with the adaptor protein RssB (purple oval). The known anti-adaptor proteins (αA; grey circle) that contribute to RpoS stabilization under different stress conditions in E. coli and Salmonella share some but not all inducing signals, and the same inducing signal (magnesium starvation via PhoQP) is used for different proteins in different species. Multiple regulatory factors (yellow ovals) control the expression of the anti-adaptors.

Figure 2. ClpC interaction with various adaptor proteins modulates substrate specificity in B. subtilis

ClpC oligomerization and interaction with ClpP depends on its interaction with adaptor proteins. A. MecA allows the degradation of ComK but is titrated, in the case of nutritional stress, by the anti-adaptor protein ComS, allowing development of competence by sparing ComK. ComS and ComK are themselves degraded by ClpCP. MecA degradation leads to ClpCP disassembly. B. McsB activity depends on its phosphorylation state but also requires ClpC phosphorylation. Under normal growth conditions, McsB kinase activity is inhibited by its interaction with ClpC. During heat shock, ClpC interacts preferentially with unfolded proteins, allowing McsB phosphorylation which is also favored by the protein McsA. This activation leads to the degradation of the repressor, CtsR. In thus far undefined conditions, the YwlE phosphatase inactivates McsB.