From magic spot ppGpp to MESH1: Stringent response from bacteria to metazoa

Abstract

All organisms are constantly exposed to varying levels of nutrients and environmental stresses. This is especially true for unicellular organisms, such as bacteria, which are exposed to perpetual changes of outside environments. Therefore, it is critical to have mechanisms to sense, adapt, and cope with various nutrient deprivations and metabolic stresses. In bacteria, one of the major stress adaptive responses is the "stringent response" [1] that enables bacteria to transition into a semi-dormant state characterized by proliferation arrest, stress survival, and metabolic/transcriptome reprogramming. The stringent response is triggered by the alarmone (p)ppGpp, also termed the magic spot which dramatically increases it level under stresses and binds to various protein targets to mediate the stringent response The (p)ppGpp level is regulated by the balance of its synthesis and degradation (hydrolysis) by the proteins in the RelA/SpoT homologues (RSHs) superfamily The best-characterized RSH proteins are the multi-domain long RHS proteins involved in the (p)ppGpp synthesis (RelA) and hydrolysis (SpoT). In addition, there are also single-domain RSH proteins known as small alarmone synthetases (SASs) or small alarmone hydrolases (SAHs) mediating the synthesis and hydrolysis of alarmones, respectively Interestingly, SAHs have been classified into multiple subgroups including the Mesh1 and Mesh1-L subfamilies However, the physiological function of these short RSH proteins is still not completely understood.

Topics & Concepts