RESUMO
Bunyavirus is widely distributed, highly contagious, and has a high fatality rate. It is a negative- strand RNA virus that has a major impact on public health around the world. The development of vaccines and the search for drugs are the key to prevent bunyavirus infection. The nucleoprotein (NP) of viruses is necessary for the synthesis of viral RNA, which combines with viral RNA to form the nucleocapsid, participates in viral assembly and RNA transcription, and plays an important role in viral proliferation. In addition, NP also has B cell and T cell epitopes, which can induce cellular and humoral immunity, so NP is an ideal target for vaccine design and drug development. Given its abundance and specificity, NP is also commonly used in the detection of viral diseases. More and more bunyavirus NP structures and structures of NP-RNA complexes have been resolved. Researchers have discovered two important antiviral targets through these structures, the terminal arm and the RNA binding cleft. This paper reviews the function and three-dimensional structure of the bunyavirus NP and the research progress of NP as an antiviral target, in order to provide a theoretical basis for the prevention and treatment of the bunyavirus disease.
RESUMO
Toxin-antitoxin system (TA) is a genetic element widely found in chromosomes and plasmids of bacteria, archaea and prophages. TA usually consists a toxin that inhibits the growth of bacteria and an antitoxin that neutralizes its toxicity. Since the discovery of the first CcdB / CcdA TA in the 1980s, TA has been proved to exist in almost all sequenced microorganisms and plays an important role in maintaining plasmid stability, anti-phage and promoting biofilm formation. At present, TA is divided into type I-VIII, among which type IITA is the most widely studied. HipBA is a type II TA. The toxin HipA in Escherichia coli HipBA is a serine / threonine kinase, which inhibits protein translation by phosphorylating bacterial Glutamyl tRNA synthetase (GltX), and its toxicity can be specifically neutralized by HipB. Recently, it has been found that Escherichia coli HipA homologous proteins exist widely in microorganisms, and they form a potential novel TA with genes of the same promoter, in which HipBST has been confirmed by experiments. The toxin HipT and the antitoxin HipS in this TA are similar to the C-terminal and N-terminal of E. coli HipA respectively, and the neutralization mechanism and the substrate of the toxin are different from that of E. coli toxin HipA. This study summarizes the recent discovery of special TA, especially the neutralization mechanism of HipBST which widely exists in prokaryotes.
RESUMO
Proteasome regulatory particles(RPs) play a vital role in many essential signaling pathways for the regulation of protein degradation and maintenance of cell homeostasis. The mechanism of eukaryotic proteasomes in cancer treatment and drug development has attracted widespread attention. Currently, three proteasome inhibitors are already in use in clinical treatments. There is continuous in-depth research on proteasome structures as well as functions using crystallography and cryo-electron microscopy. Recently, the atomic structure of three types of RPs has been resolved. Type 1 is conservative RP 19S (PA700). Type 2 is the 11S RP PA28 (PA28α, PA28β, PA28γ) and PA26. Type 3 is a conservative Blm10/PA200 proteasome RP. The Type 1 proteasome RP carries out protein degradation activity in an ATP-dependent manner, types 2 and 3 function in an ATP-independent manner. By studying the structure and function of three different types of proteasome RPs, the mechanism of proteasome activity was clarified and the development of inhibitors based on the structure was promoted. Based on the structural biology research of proteasome RPs, this article systematically summarizes the structural biological characteristics of the three types of proteins and the research progress of their mechanisms of regulation of different cellular processes. This will increase our knowledge about proteasome research developments and will provide important reference information for drug design in cancer treatment.
