Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0276640 (TEM)
 20,729 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 14-3-3s are a family of dimeric evolutionary conserved pSer/pThr binding proteins that play a key role in multiple biological processes by interacting with a plethora of client proteins. Giardia duodenalis is a flagellated protozoan that affects millions of people worldwide causing an acute and chronic diarrheal disease. The single giardial 14-3-3 isoform (g14-3-3), unique in the 14-3-3 family, needs the constitutive phosphorylation of Thr214 and the polyglycylation of its C-terminus to be fully functional in vivo. Alteration of the phosphorylation and polyglycylation status affects the parasite differentiation into the cyst stage. To further investigate the role of these post-translational modifications, the crystal structure of the g14-3-3 was solved in the unmodified apo form. Oligomers of g14-3-3 were observed due to domain swapping events at the protein C-terminus. The formation of filaments was supported by TEM. Mutational analysis, in combination with native PAGE and chemical cross-linking, proved that polyglycylation prevents oligomerization. In silico phosphorylation and molecular dynamics simulations supported a structural role for the phosphorylation of Thr214 in promoting target binding. Our findings highlight unique structural features of g14-3-3 opening novel perspectives on the evolutionary history of this protein family and envisaging the possibility to develop anti-giardial drugs targeting g14-3-3.
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PMID:The crystal structure of Giardia duodenalis 14-3-3 in the apo form: when protein post-translational modifications make the difference. 2465 79

It has been reported that the immune response mediated by T CD8+ lymphocytes plays a critical role in the control of Trypanosoma cruzi infection and that the clinical symptoms of Chagas disease appear to be related to the competence of the CD8+ T immune response against the parasite. Herewith, in silico prediction and binding assays on TAP-deficient T2 cells were used to identify potential HLA-A*02:01 ligands in the T. cruzi TcCA-2 protein. The TcCA-2-specific CD8+ T cells were functionality evaluated by Granzyme B and cytokine production in peripheral blood mononuclear cells (PBMC) from Chagas disease patients stimulated with the identified HLA-A*02:01 peptides. The specific cells were phenotypically characterized by flow cytometry using several surface markers and HLA-A*02:01 APC-labeled dextramer loaded with the peptides. In the T. cruzi TcCA-2 protein four T CD8+ epitopes were identified which are processed and presented during Chagas disease. Interestingly, a differential cellular phenotypic profile could be correlated with the severity of the disease. The TcCA-2-specific T CD8+ cells from patients with cardiac symptoms are mainly effector memory cells (TEM and TEMRA) while, those present in the asymptomatic phase are predominantly naive cells (TNAIVE). Moreover, in patients with cardiac symptoms the percentage of cells with senescence features is significantly higher than in patients at the asymptomatic phase of the disease. We consider that the identification of these new class I-restricted epitopes are helpful for designing biomarkers of sickness pathology as well as the development of immunotherapies against T. cruzi infection.
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PMID:Differential phenotypic and functional profiles of TcCA-2 -specific cytotoxic CD8+ T cells in the asymptomatic versus cardiac phase in Chagasic patients. 2581 96

Bacteriophages and engineered nano-material (AgNPS) interactions is a relatively unexplored area of research. To answer the fundamental question whether bacteriophage lytic growth cycle is affected by the presence of AgNPs, laboratory experiments were performed with phages of Klebsiella pneumoniae, Delftia tsuruhatensis, Salmonella typhimurium, and Shigella flexneri using silver nanoparticles (AgNPs) with coating materials. One-step growth curves of bacteriophages indicated that the presence of these nanoparticles, and the associated ions of silver, produced pronounced effects on the lytic infection of certain bacteriophages. Effects included 96% reductions in post-infection phage yield in terms of plaque forming units (PFUs) after phages were incubated with silver nanoparticles and 28%-43% reductions from the presence of Ag+ alone. However, when Klebsiella pneumonia phage KL and Salmonella typhimurium phage Det7 were exposed to silver nanoparticles coated with poly-N-vinyl-2 pyrrolidone (PVP), an increase in final phage yield by as much as 250% was observed compared with the same phage not incubated with nanoparticles. A proposed mechanism, observed by transmission electron microscopy and verified using synthetic biology by which the nanoparticle binding phenotype can be produced, is that the binding of metal nanomaterial to phage virions results in potentially inhibitory effects. This binding was found to be dependent on the presence of exposed positively charged C-terminal amino-acid residues on the phage capsid surface, implied at first by amino-acid sequence comparisons between capsid proteins of the different phages used in this study. This was then proven experimentally using targeted DNA editing methods to fuse positive charged amino-acid residues to the coat protein C-terminus of non-binding phage. This induced the AgNP binding phenotype, as observed by TEM, DLS size measurements, and growth curve data that show the mutant constructs to be functionally inhibited after exposure to AgNPs. This research sets up a first platform for further research in the unexplored area of phage and AgNP interactions and provides useful findings.
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PMID:Evaluating the effect of silver nanoparticles on bacteriophage lytic infection cycle-a mechanistic understanding. 3250 9