The Universally Conserved Prokaryotic GTPases

Abstract

SUMMARY Members of the large superclass of P-loop GTPases share a core domain with a conserved three-dimensional structure. In eukaryotes, these proteins are implicated in various crucial cellular processes, including translation, membrane trafficking, cell cycle progression, and membrane signaling. As targets of mutation and toxins, GTPases are involved in the pathogenesis of cancer and infectious diseases. In prokaryotes also, it is hard to overestimate the importance of GTPases in cell physiology. Numerous papers have shed new light on the role of bacterial GTPases in cell cycle regulation, ribosome assembly, the stress response, and other cellular processes. Moreover, bacterial GTPases have been identified as high-potential drug targets. A key paper published over 2 decades ago stated that, “It may never again be possible to capture [GTPases] in a family portrait” (H. R. Bourne, D. A. Sanders, and F. McCormick, Nature 348 :125-132, 1990) and indeed, the last 20 years have seen a tremendous increase in publications on the subject. Sequence analysis identified 13 bacterial GTPases that are conserved in at least 75% of all bacterial species. We here provide an overview of these 13 protein subfamilies, covering their cellular functions as well as cellular localization and expression levels, three-dimensional structures, biochemical properties, and gene organization. Conserved roles in eukaryotic homologs will be discussed as well. A comprehensive overview summarizing current knowledge on prokaryotic GTPases will aid in further elucidating the function of these important proteins.

Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1

“…The YchF/Ola1 subfamily constitutes one of the most conserved members of the P-Loop GTPase family and is characterized by its unique preference for ATP (24,52). Sequence comparison between E. coli YchF and human hOla1 revealed 45% sequence identity and 62% sequence similarity, but there is so far no clear consensus about the possible role of this protein family.…”

“…The associated conformational changes then determine complex protein interaction networks that regulate essential processes such as protein synthesis, cellular differentiation, or stress response (52,54). At least 20 GTPase families have been identified based on structural features and eight of these families are universally conserved in eukaryotes, bacteria, and archaea.…”

Hypothesis: type I toxin–antitoxin genes enter the persistence field—a feedback mechanism explaining membrane homoeostasis

“…The model is outlined in figure 4. During rapid cell growth, when energy and growth substrates are plentiful, the membrane potential [67]. The hokB/sokB locus produces hokB mRNA and SokB antisense RNA that inhibits translation of the truncated form of hokB mRNA.…”

“…However, during stress, Obg and ( p)ppGpp stimulate transcription of hok, thereby leading to accumulation of hokB mRNA, which, in turn, overrides the inhibition by SokB-RNA, thus leading to HokB synthesis and to depolarization of the inner cell membrane. Membrane depolarization has two effects: it leads to increased persistence [67] and hypothetically leads to detachment of RNase E from the membrane that, in turn, leads to reduced degradation of SokB-RNA. Accumulation of SokB-RNA inhibits translation of truncated hokB mRNA, thus establishing a negative, homoeostatic control loop that prevents irreversible membrane damage and cell killing.…”

GTPases: Prerequisite Molecular Target in Virulence and Survival of Mycobacterium Tuberculosis

“…According to the reports it has been stated that these core GTPases are either involved in ribosomal function or signal transmission [5]. These core GTPases protein are elongation factor G (Ef-G), elongation factor Tu (Ef-Tu), initiation factor 2 (If-2), YihA, LepA, Thd F/ Trm E, Ffh, FtsY, Obg, Era, EngA, Der and Ych F that are found in prokaryotes and are involved basically in ribosomal functions [6]. In many bacteria several GTPases among these are very important for cell viability itself.…”