Two-component signal transduction in Bacillus subtilis: how one organism sees its world.

Abstract

Variability and adaptability are crucial characteristics of organisms possessing the ability to survive and prosper in a wide variety of environmental conditions. The most adaptable bacteria contain a large reservoir of genetic information encoding biochemical pathways designed to cope with a variety of environmental situations. Organisms that have the genetic capability to respond to altered conditions do so when stimulated by specific signals. Recognition of specific signals and conversion of this information into specific transcriptional or behavioral responses is the essence of signal transduction. A mechanism commonly found in bacteria for signal transduction is the two-component system (23, 26). Its basis is the conversion of signal recognition to a chemical entity, i.e., a phosphoryl group, that modifies the functional activity of proteins. Signal recognition and transduction are the province of the sensor histidine kinase component of the system. This protein has separable sensor and histidine phosphotransferase domains that function to recognize (bind) the signal, causing the kinase to autophosphorylate a histidine residue of the phosphotransferase domain (Fig. ​(Fig.1).1). The phosphoryl group is subsequently transferred to the second component protein, the response regulator, where it resides as an acyl phosphate of an aspartic acid residue. The response regulator consists of the phosphorylatable aspartate domain and an output domain that is activated to carry out its function by conformational or, perhaps, electrostatic alterations induced by the phosphoryl group. In most cases, the response regulator is a transcription activator for genes whose products are specifically utilized to respond to the unique nature of a given input signal. In the chemotaxis system of bacteria, the response regulator determines the direction of rotation of the flagellar motor. The basics of the signal transduction mechanism remain the same regardless of the input signal or the function of the response regulator. FIG. 1 Schematic view of two-component and phosphorelay systems. Activation signals recognized by sensor domains of histidine kinases result in autophosphorylation of a histidine in the histidine phosphotransferase domain (His PTase). The phosphoryl group (P) ... This phosphoryl group-based signal transduction mechanism exists in two major conformations in microorganisms: the two-component system and a four-component system termed the phosphorelay (Fig. ​(Fig.1).1). Signal interpretation and transduction by histidine kinases are the same in both, but the target of the kinase in a phosphorelay is a single-domain response regulator consisting of only the phosphorylated aspartate domain. This phosphorylated protein serves as a substrate for a phosphotransferase that transfers the phosphoryl group to a response regulator-transcription factor. The phosphotransferase is transiently phosphorylated on a histidine during this process. In a phosphorelay, the phosphoryl group is transferred in the order His-Asp-His-Asp, which differs from the His-Asp series of a two-component system. In the first-discovered phosphorelay used to initiate sporulation in Bacillus subtilis, all of the components (domains) reside on different proteins (4). Subsequently discovered phosphorelays in bacteria, fungi, and plants use composite proteins where the kinase and first response regulator domain and sometimes the phosphotransferase domain are contiguous within a single polypeptide chain (1, 6). The sporulation initiation phosphorelay is a signal integration circuit that processes both positive and negative signals, which suggests that phosphorelays are used where a number of opposing signals must be interpreted by the signal transduction system (22).