Insights into peptidyl-prolyl cis–trans isomerase structure and function in immunocytes

Nath, Pulak; Isakov, Noah

doi:10.1016/j.imlet.2014.11.002

Cited by 39 publications

(29 citation statements)

References 187 publications

(155 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While after treatment with (CS and OA using 0/0 h) CYPA was not detectable, suggesting that its expression is very sensitive to the treatment. Where the enhanced apoptosis be brought about may be the result of OA’s signalling inhibitory mechanism and its ROS production that have modulated CYPA activities of antioxidant stabilization, transcriptional control, trafficking, cell cycle regulation and signal transduction [ 42 ]. Thus, the results suggest that there is a strong correlation between CYPA expression and apoptosis; thus the chosen treatments can serve as potential approaches to overcome drug resistance associated with atypical CYPA expression.…”

Section: Discussionmentioning

confidence: 99%

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models

Althurwi

Beale

et al. 2020

IJMS

View full text Add to dashboard Cite

In the present study, cisplatin, artemisinin, and oleanolic acid were evaluated alone, and in combination, on human ovarian A2780, A2780ZD0473R, and A2780cisR cancer cell lines, with the aim of overcoming cisplatin resistance and side effects. Cytotoxicity was assessed by MTT reduction assay. Combination index (CI) values were used as a measure of combined drug effect. MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis were used to identify protein biomarkers in ovarian cancer and to evaluate combination effects. Synergism from combinations was dependent on concentration and sequence of administration. Generally, bolus was most synergistic. Moreover, 49 proteins differently expressed by 2 ≥ fold were: CYPA, EIF5A1, Op18, p18, LDHB, P4HB, HSP7C, GRP94, ERp57, mortalin, IMMT, CLIC1, NM23, PSA3,1433Z, and HSP90B were down-regulated, whereas hnRNPA1, hnRNPA2/B1, EF2, GOT1, EF1A1, VIME, BIP, ATP5H, APG2, VINC, KPYM, RAN, PSA7, TPI, PGK1, ACTG and VDAC1 were up-regulated, while TCPA, TCPH, TCPB, PRDX6, EF1G, ATPA, ENOA, PRDX1, MCM7, GBLP, PSAT, Hop, EFTU, PGAM1, SERA and CAH2 were not-expressed in A2780cisR cells. The proteins were found to play critical roles in cell cycle regulation, metabolism, and biosynthetic processes and drug resistance and detoxification. Results indicate that appropriately sequenced combinations of cisplatin with artemisinin (ART) and oleanolic acid (OA) may provide a means to reduce side effects and circumvent platinum resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models

Althurwi

Beale

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Because prokaryotes and eukaryotes are known to have three ubiquitously distributed enzymes known as cyclophilins, FK506 binding proteins (FKBPs), and parvulins, which catalyze the cis/trans isomerization of peptide bonds preceding prolyl residues, thereby assisting protein folding at the post-translocational level (Ünal and Steinert, 2014; Nath and Isakov, 2015). We found that SS2-PrsA expressed in E. coli showed dose-dependent cytotoxicity with significant cell death at concentrations above 75 μg/ml.…”

Section: Discussionmentioning

confidence: 99%

Roles of the Putative Type IV-like Secretion System Key Component VirD4 and PrsA in Pathogenesis of Streptococcus suis Type 2

Jiang

Yang

Zhou

et al. 2016

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Streptococcus suis type 2 (SS2) is a zoonotic pathogen causing septic infection, meningitis and pneumonia in pigs and humans. SS2 may cause streptococcal toxic shock syndrome (STSS) probably due to excessive release of inflammatory cytokines. A previous study indicated that the virD4 gene in the putative type IV-like secretion system (T4SS) within the 89K pathogenicity island specific for recent epidemic strains contributed to the development of STSS. However, the functional basis of VirD4 in STSS remains unclear. Here we show that deletion of virD4 led to reduced virulence as shown by about 65% higher LD50, lower bacterial load in liver and brain, and lower level of expression of inflammatory cytokines in mice and cell lines than its parent strain. The ΔVirD4 mutant was more easily phagocytosed, suggesting its role as an anti-phagocytic factor. Oxidative stress that mimic bacterial exposure to respiratory burst of phagocytes upregulated expression of virD4. Proteomic analysis identified 10 secreted proteins of significant differences between the parent and mutant strains under oxidative stress, including PrsA, a peptidyl-prolyl isomerase. The SS2 PrsA expressed in E. coli caused a dose-dependent cell death and increased expression of proinflammatory IL-1β, IL-6 and TNF-α in murine macrophage cells. Our data provide novel insights into the contribution of the VirD4 factor to STSS pathogenesis, possibly via its anti-phagocytic activity, upregulation of its expression upon oxidative stress and its involvement in increased secretion of PrsA as a cell death inducer and proinflammatory effector.

show abstract

“…Prolines preceded by aromatic residues such as tyrosine or phenylalanine, or another proline, are more likely to adopt cis conformation. 5,10 Proline isomerization forms the basis of some molecular allosteric switches 10,11 and timers, 12 and plays a role in different physiological (e.g., immune function, 13 cell signaling [14][15][16][17] ) and pathological conditions (e.g., cancer, [18][19][20][21] Alzheimer's disease 18,22 ). In a classical antibody structure, prolines can be found both in constant and variable regions.…”

Section: Introductionmentioning

confidence: 99%

The impact of proline isomerization on antigen binding and the analytical profile of a trispecific anti-HIV antibody

Masiero

Lechat

Marianne

et al. 2020

mAbs

View full text Add to dashboard Cite

Proline cis-trans conformational isomerization is a mechanism that affects different types of protein functions and behaviors. Using analytical characterization, structural analysis, and molecular dynamics simulations, we studied the causes of an aberrant two-peak size-exclusion chromatography profile observed for a trispecific anti-HIV antibody. We found that proline isomerization in the tyrosine-proline-proline (YPP) motif in the heavy chain complementarity-determining region (CDR)3 domain of one of the antibody arms (10e8v4) was a component of this profile. The pH effect on the conformational equilibrium that led to these two populations was presumably caused by a histidine residue (H147) in the light chain that is in direct contact with the YPP motif. Finally, we demonstrated that, due to chemical equilibrium between the cis and trans proline conformers, the antigen-binding potency of the trispecific anti-HIV antibody was not significantly affected in spite of a potential structural clash of 10e8v4 YP trans P trans conformers with the membrane-proximal ectodomain region epitope in the GP41 antigen. Altogether, these results reveal at mechanistic and molecular levels the effect of proline isomerization in the CDR on the antibody binding and analytical profiles, and support further development of the trispecific anti-HIV antibody.

show abstract

Insights into peptidyl-prolyl cis–trans isomerase structure and function in immunocytes

Cited by 39 publications

References 187 publications

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models

Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour Models

Roles of the Putative Type IV-like Secretion System Key Component VirD4 and PrsA in Pathogenesis of Streptococcus suis Type 2

The impact of proline isomerization on antigen binding and the analytical profile of a trispecific anti-HIV antibody

Contact Info

Product

Resources

About