Sharif Digital Repository

Backgrounds In order to move towards the elimination and eradication of malaria in the world, the development of vaccines is inevitable. Many modern vaccines are based on recombinant technology; however, they may not provide a fully protective, long-lasting immune response. One of the strategies to improve recombinant vaccines is designing the nanovaccines such as self-assembling protein nanoparticles (SAPNs). Hence, the presentation of epitopes in a repeat array and correct conformation should be considered. P. falciparum generative cell-specific 1 (PfGCS1) is a main transmission-blocking vaccine candidate with two highly conserved fragments, HAP2-GCS1 and cd loop, inducing partial malaria... 

Pichia pastoris is used extensively as a production platform for many recombinant proteins. The dissolved oxygen (DO) is one of the most important factors influencing protein production. The influence of the DO on productivity has not been studied independent from the feed rate. In this work, various DO levels were investigated independent from the feed rate. The model system was recombinant P. pastoris under the control of methanol-induced alcohol oxidase promoter, which expressed HRP as the target protein. No significant effect was observed in terms of titer and specific productivity, which is a confirmation of the fact that the DO in a one-compartment system cannot boost productivity for... 

Hepcidin is a peptide hormone that plays an important role in iron metabolism. We have produced a recombinant mouse hepcidin-1 by using baculovirus expression system. Its expression yield was 25 μg/ml when cell culture media were supplemented with a protease inhibitor cocktail. The recombinant mouse hepcidin-1 and synthetic human hepcidin-25 had similar effects on reducing ferroportin expression in J774A cell line and in peritoneal macrophages. However, synthetic human hepcidin-25 was more efficient than recombinant mouse hepcidin-1 in reducing iron concentration in blood circulation (p < 0.01)  

We carry out a coarse-grained molecular dynamics simulation of phospholipid vesicles with transmembrane proteins. We measure the mean and Gaussian curvatures of our protein-embedded vesicles and quantitatively show how protein clusters change the shapes of their host vesicles. The effects of depletion force and vesiculation on protein clustering are also investigated. By increasing the protein concentration, clusters are fragmented to smaller bundles, which are then redistributed to form more symmetric structures corresponding to lower bending energies. Big clusters and highly aspherical vesicles cannot be formed when the fraction of protein to lipid molecules is large  

Protein aggregation in cell membrane is vital for the majority of biological functions. Recent experimental results suggest that transmembrane domains of proteins such as α-helices and β-sheets have different structural rigidities. We use molecular dynamics simulation of a coarse-grained model of protein-embedded lipid membranes to investigate the mechanisms of protein clustering. For a variety of protein concentrations, our simulations under thermal equilibrium conditions reveal that the structural rigidity of transmembrane domains dramatically affects interactions and changes the shape of the cluster. We have observed stable large aggregates even in the absence of hydrophobic mismatch,... 

Recent studies have provided clues for participation of apoptosis related genes in the development of periodontitis. We examined expression of four apoptosome related genes namely CPSF7, AGO2, WDR33 and HUR1 in the blood and tissues of patients with stage III-IV periodontitis compared with control blood/tissue samples. Expression of AGO2 was significantly higher in the blood specimens of individual having periodontitis compared with healthy persons (ratio of mean expression = 6.9, P value = 4.79E−02). However, when categorizing individuals based on their gender, none of comparisons yielded significant results. Expression of AGO2 was not different between tissue samples of patients and... 

Background: Flagellin of Salmonella enterica serovar Enteritidis (SEF) stimulates immune responses to both itself and coapplied antigens. It is therefore used in vaccine development and immunotherapy. Removal of pathogenic S. enterica ser. Enteritidis from SEF production process is advantageous due to the process safety improvement. The protein solubility analysis using SDS-PAGE indicated that 53.49% of SEF expressed in Escherichia coli formed inclusion bodies. However, the protein recovery from inclusion bodies requires a complex process with a low yield. Objective: We thus aim to study possibility of enhancing SEF expression in E. coli in soluble form using chemical and molecular... 

Upon incorporation of nanoparticles (NPs) into the body, they are exposed to biological fluids, and their interaction with the dissolved biomolecules leads to the formation of the so-called protein corona on the surface of the NPs. The composition of the corona plays a crucial role in the biological fate of the NPs. While the effects of various physicochemical parameters on the composition of the corona have been explored in depth, the role of temperature upon its formation has received much less attention. In this work, we have probed the effect of temperature on the protein composition on the surface of a set of NPs with various surface chemistries and electric charges. Our results... 

Axon is an important part of the neuronal cells and axonal microtubules are bundles in axons. In axons, microtubules are coated with microtubule-associated protein tau, a natively unfolded filamentous protein in the central nervous system. These proteins are responsible for cross-linking axonal microtubule bundles. Through complimentary dimerization with other tau proteins, bridges are formed between nearby microtubules creating bundles. Formation of bundles of microtubules causes their transverse reinforcement and has been shown to enhance their ability to bear compressive loads. Though microtubules are conventionally regarded as bearing compressive loads, in certain circumstances during... 

Interleukin 1 Receptor type I (IL-1RI) is a multi-domain transmembrane receptor that triggers the inflammatory response. Understanding its detailed mechanism of action is crucial for treating immune disorders. IL-1RI is activated upon formation of its functional assembly that occurs by binding of the IL-1 cytokine and the accessory protein (Il-1RAcP) to it. X-ray crystallography, small-Angle X-ray Scattering and molecular dynamics simulation studies showed that IL-1RI adopts two types of ‘compact’ and ‘extended’ conformational states in its dynamical pattern. Furthermore, glycosylation has shown to play a critical role in its activation process. Here, classical and accelerated atomistic... 

Background: Study of nanostructure-protein interaction for development of various types of nano-devices is very essential. Among carbon nanostructures, carbon nanotube (CNT) provides a suitable platform for functionalization by proteins. Previous studies have confirmed that the CNT induces changes in the protein structure. Methods: Molecular dynamics (MD) simulation study was employed to illustrate the changes occurring in the protein G (PGB) in the presence of a CNT. In order to predict the PGB surface patches for the CNT, Autodock tools were utilized. Results: Docking results indicate the presence of two different surface patches with diverse amino acids: the dominant polar residues in the... 

Background: It has been previously shown that palindromic sequences are frequently observed in proteins. However, our knowledge about their evolutionary origin and their possible importance is incomplete. Results: In this work, we tried to revisit this relatively neglected phenomenon. Several questions are addressed in this work. (1) It is known that there is a large chance of finding a palindrome in low complexity sequences (i.e. sequences with extreme amino acid usage bias). What is the role of sequence complexity in the evolution of palindromic sequences in proteins? (2) Do palindromes coincide with conserved protein sequences? If yes, what are the functions of these conserved segments?... 

Due to their ultra-small size, nanoparticles (NPs) have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. NPs are recognized as promising and powerful tools to fight against the human brain diseases such as multiple sclerosis or Alzheimer's disease. In this review, after an introductory part on the nature of protein fibrillation and the existing approaches for its investigations, the effects of NPs on the fibrillation process have been considered. More specifically, the role of biophysicochemical properties of NPs, which define their affinity for protein monomers, unfolded monomers,... 

A novel combination of discontinuous molecular dynamics and the Langevin equation, together with an intermediate-resolution model of proteins, is used to carry out long (several microsecond) simulations in order to study transport of proteins in nanopores. We simulated single-domain proteins with the α-helical native structure. Both attractive and repulsive interaction potentials between the proteins and the pores' walls are considered. The diffusivity D of the proteins is computed not only under the bulk conditions but also as a function of their "length" (the number of the amino-acid groups), temperature T, pore size, and interaction potentials with the walls. Compared with the... 

Signal Transducer and Activator of Transcription (STAT) pathway is functionally located downstream of Janus kinases proteins and can integrate signals from diverse pathways, thus regulating several aspects of immune responses. Although contribution of STAT proteins in the pathogenesis of several inflammatory conditions has been confirmed, their role in the development of periodontitis has been less appraised. Thus, we assessed levels of STAT transcripts in the periodontal tissues and circulation of affected individuals compared with the corresponding controls. Expression of STAT1 was remarkably lower in tissues samples of patients compared with control tissues (Ratio of mean expression (RME)... 

SARS-CoV-2 is a strain of Coronavirus family that caused the ongoing pandemic of COVID-19. Several studies showed that the glycosylation of virus spike (S) protein and the Angiotensin-Converting Enzyme 2 (ACE2) receptor on the host cell is critical for the virus infectivity. Molecular Dynamics (MD) simulations were used to explore the role of a novel mutated O-glycosylation site (D494S) on the Receptor Binding Domain (RBD) of S protein. This site was suggested as a key mediator of virus-host interaction. By exploring the dynamics of three O-glycosylated models and the control systems of unglcosylated S4944 and S494D complexes, it was shown that the decoration of S494 with elongated O-glycans... 

Background: Codon degeneracy and codon usage by organisms is an interesting and challenging problem. Researchers demonstrated the relation between codon usage and various functions or properties of genes and proteins, such as gene regulation, translation rate, translation efficiency, mRNA stability, splicing, and protein domains. Researchers usually represent segments of proteins responsible for specific functions or structures in a family of proteins as sequence patterns or motifs. We asked the question if organisms use the same codons in pattern segments as compared to the rest of the sequence. Methods. We used the likelihood ratio test, Pearson's chi-squared test, and mutual information... 

Graphene oxide nanoribbons (GONRs) were synthesized using an oxidative unzipping of multi-walled carbon nanotubes. The interactions of the GONRs with various concentrations of fetal bovine serum or human plasma serum indicated that the GONRs were functionalized substantially by the albumin originated from the two different protein sources. Then, concentration-dependent cytotoxicity of the protein-functionalized GONRs on human epithelial cells was studied. Although the GONRs with concentrations ≤50 μg/mL did not exhibit significant cytotoxicity on the cells (with the cell viability >85%), the concentration of 100 μg/mL exhibited significant cytotoxicity including prevention of cell...