Universal stress protein

The universal stress protein (USP) domain is a superfamily of conserved genes which can be found in bacteria, archaea, fungi, protozoa and plants. Proteins containing the domain are induced by many environmental stressors such as nutrient starvation, drought, extreme temperatures, high salinity, and the presence of uncouplers, antibiotics and metals. In the presence of these stressors, Usp genes are upregulated resulting in large quantities of Usp proteins being produced by the cell. The over production of USP genes allows the organisms to better cope with stresses by largely unknown mechanisms. However, the USPs will alter the expression of a variety of genes that help to cope with stress.

Function

The primary function of this superfamily is to protect the organism from environmental stress such as exposure to UV light, which may induce genes containing the USP domain in order to protect the DNA and more generally the cell from further damage. During bacterial starvation the USP genes upregulated will often arrest cell growth and promote its metabolism to adapt to sparse nutrients. Recent research also suggests proteins containing this domain have functions beyond the realms of dealing with environmental stresses. Nachin et al. demonstrated in Escherichia coli that USPs are involved in actions such as adhesion and motility. The researchers, through means of "knocking out" USP genes known as UspE and UspC, saw results suggesting an inability to swim and completely lack of motility, respectively. Conversely, mutants for genes UspF and UspG were shown to have enhanced swimming abilities. Therefore, mobility is affected both positively and negatively USPs within E. coli. This demonstrates USPs influence throughout the cell could be widespread for a number of reasons. Additionally, in Halmonas elongate, there is a USP called TeaD has been described as a key regulator in the transport of Ectoine across the cell membrane. This demonstrates how versatile USPs can be. Their function, while primarily encompasses increasing survival during stressful conditions, is not always limited to this.

Evolution The ubiquitous nature of these proteins suggests the domain evolved in an ancestral species as well as highlighting the clear biological significance these proteins have in order to still be present in the three domains of life. It has been suggested that the USP A domain was part of an ancient protein family. This is due to the similarity in structure between many distantly related organisms. Aravind et al. confirmed these ideas with extensive evolutionary analysis. Aravind suggested that these proteins were part of a much larger protein structural family which was present and diversified in our last universal common ancestor for all extant life. The original function has been suggested to be a nucleotide binding domain which was implicated in signal transduction

Structure As the USP domain is widespread across many organisms, there is great diversity in the structures of these proteins. For Haemophilus influenzae, its UspA resides in the cytoplasm. The protein forms an asymmetric dimer with characteristic alpha and beta fold structures. There are differences among different bacteria in areas such as ATP binding sites. In this case, UspA does not have ATP binding activity. Generally, USPs form dimers and have domains for nucleotide binding activity. However, as it is such a diverse group, often with little known about the exact structure, it's not possible to comment on each USP. In addition to this, UspA may reside in different areas of the cell. For example, in this case it was in the cytoplasm but for others, it may be in the cell membrane.

Bacteria Much of the research into USP is done on bacteria, specifically E. coli (Strain K-12). Consequently, much is known about the USP domains in bacteria. In E. coli there are six families of USP domains which are present in more than 1000 different proteins. The six families are Usp A, -C, -D, -E, -F and –G which are triggered by differing environmental insults and often act via varying mechanisms. UspA is the most commonly studied USP due to its widespread presence within bacterial genomes. UspA is especially implicated in the resistance of a huge number of stressors most notably tetracycline exposure and high temperatures, with the exception of not forming a response to cold shock. It is thought UspA is especially important to the recovery of E. coli following starvation of nutrients. UspA during normal growth conditions does not seem to influence gene expression. However, during stressful conditions such as carbon starvation, UspA has been shown to have a global influence on gene expression. A proposed mechanism for such a change in gene expression is that UspA has been suggested to bind to DNA. When UspA is mutated, E. coli becomes far more vulnerable UV induced DNA damage. It's important to note the USP responses are independent of many other stress responses seen in bacteria such as rpoS.

The induction of USP proteins have also been implicated in transitions not only in metabolism or growth but in changes in the colonies' entire phenotype. Bacterial colonies can produce formations known as biofilms. Zhang and colleagues demonstrated that USPs may be involved in the promotion of intertidal biofilms. They observed that during stressful conditions involving metal ions and oxidative stresses that the biofilm phenotype would form. Upon analysis of these biofilms, it could be seen that there was a greatly upregulated level of UspA which Zhang suggests, may be involved with induction of biofilm formation. It is thought UspA may be involved in signalling processes which will upregulate genes involved with biofilm production. With findings such as these, it's beginning to be accepted that USPs are acting using an extremely wide range of mechanisms to ensure cell survival.

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