The interaction of amyloid beta (Aβ) peptides with the cell membrane is one of the factors enhancing Aβ aggregation, which is closely related to neurodegenerative disease. In this work, we performed molecular dynamics (MD) simulation to investigate the initial stage of adhesion of Aβ to a GM1 ganglioside-containing membrane. Conformational change of Aβ due to interaction with the membrane was monitored and compared with that of Aβ observed in the previous study. Multiple computational trials were executed to analyze the probability of Aβ binding using a calculation model consisting of a GM1-containing mixed lipid membrane, a water layer, ions, and Aβ. A single long-time MD simulation was also carried out. It was suggested from the simulation that a cluster of sialic acids of GM1 head groups often caught the side chain of His13 or His14 of Aβ in the early stage of the MD simulations. Afterward, the main chain of Leu34 formed many hydrogen bonds with gangliosides. These residues cooperatively work for Aβ to be held on the lipid membrane. It is notable that Aβ was observed to be deeply inserted into the head group region of the lipid membrane in some computational trials. In the insertion, Aβ occasionally formed a hydrogen bond with sphingomyelin. The difference in the secondary structure between Aβ and Aβ was an important factor for Aβ to be deeply inserted into the membrane.
The possible role of chitinase in in vitro growth inhibition of the wheat pathogens Fusarium graminearum and Bipolaris sorokiniana by Bacillus pumilus SG2 was investigated. B. pumilus SG2, a chitinolytic bacterium producing two different chitinases, was previously isolated from the saline deserts of Iran. When grown in Spizizen salts medium with colloidal chitin, B. pumilus SG2 secreted two chitinases into the medium, resulting in growth inhibition of F. graminearum and abortion of hyphal elongation of B. sorokiniana. In contrast, when glucose was used as the carbon source, the chitinases were not expressed and antifungal activity of the B. pumilus SG2 was completely abolished. These results confirmed that expression of the B. pumilus SG2 chitinases is under the control of two types of regulation, special regulation by chitin and global regulation by glucose. We demonstrated that chitinases are the main components that caused hyphal inhibition activity of B. pumilus SG2. Hyphal inhibition of F. graminearum and B. sorokiniana was stable in agar for a minimum of 14 days.
Background: little is known about the forecasting of new variants of SARS-COV-2 in North America and the interaction of variants with vaccine-derived neutralizing antibodies. Methods: the affinity scores of the spike receptor-binding domain (S-RBD) of B.1.1.7, B. 1.351, B.1.617, and P.1 variants in interaction with the neutralizing antibody (CV30 isolated from a patient), and human angiotensin-converting enzyme 2 (hACE2) receptor were predicted using the template-based computational modeling. From the Nextstrain global database, we identified prevalent mutations of S-RBD of SARS-CoV-2 from December 2019 to April 2021. Pre- and post-vaccination time series forecasting models were developed based on the prediction of neutralizing antibody affinity scores for S-RBD of the variants. Results: the proportion of the B.1.1.7 variant in North America is growing rapidly, but the rate will reduce due to high affinity (~90%) to the neutralizing antibody once herd immunity is reached. Currently, the rates of isolation of B. 1.351, B.1.617, and P.1 variants are slowly increasing in North America. Herd immunity is able to relatively control these variants due to their low affinity (~70%) to the neutralizing antibody. The S-RBD of B.1.617 has a 110% increased affinity score to the human angiotensin-converting enzyme 2 (hACE2) in comparison to the wild-type structure, making it highly infectious. Conclusion: The newly emerged B.1.351, B.1.617, and P.1 variants escape from vaccine-induced neutralizing immunity and continue circulating in North America in post- herd immunity era. Our study strongly suggests that a third dose of vaccine is urgently needed to cover novel variants with affinity scores (equal or less than 70%) to eliminate developing viral mutations and reduce transmission rates.
Bacillus pumilus SG2, a halotolerant strain, expresses two major chitinases designated ChiS and ChiL that were induced by chitin and secreted into the supernatant. The present work aimed to obtain a mutant with higher chitinolytic activity through mutagenesis of Bacillus pumilus SG2 using a combination of UV irradiation and nitrous acid treatment. Following mutagenesis and screening on chitin agar and subsequent formation of halos, the mutated strains were examined for degradation of chitin under different conditions. A mutant designated AV2-9 was selected owing to its higher chitinase activity. To search for possible mutations in the whole operon including ChiS and ChiL, the entire chitinase operon, including the intergenic region, promoter, and two areas corresponding to the ChiS and ChiL ORF, was suquenced. Nucleotide sequence analysis of the complete chitinase operon from the SG2 and AV2-9 strains showed the presence of a mutation in the catalytic domain (GH18) of chitinase (ChiL). The results demonstrated that a single base change had occurred in the ChiL sequence in AV2- 9. The wild-type chitinase, ChiL, and the mutant (designated ChiLm) were cloned, expressed, and purified in E. coli. Both enzymes showed similar profiles of activity at different ranges of pH, NaCl concentration, and temperature, but the mutant enzyme showed approximately 30% higher catalytic activity under all the conditions tested. The results obtained in this study showed that the thermal stability of chitinase increased in the mutant strain. Bioinformatics analysis was performed to predict changes in the stability of proteins caused by mutation.
The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic pathogen that has rapidly mutated and become transmissible to humans. There is little existing data on the mutations in SARS-CoV-2 and the impact of these polymorphisms on its transmission and viral load. In this study, the SARS-CoV-2 genomic sequence was analyzed to identify variants within the 3’UTR region of its cis-regulatory RNA elements. A 43-nucleotide genetic element with a highly conserved stem-loop II-like motif (S2M), was discovered. The research revealed 32 G>U and 16 G>U/A mutations located within the S2M sequence in human SARS-CoV-2 models. These polymorphisms appear to make the S2M secondary and tertiary structures in human SARS-CoV-2 models less stable when compared to the S2M structures of bat/pangolin models. This grants the RNA structures more flexibility, which could be one of its escape mechanisms from host defenses or facilitate its entry into host proteins and enzymes. While this S2M sequence may not be omnipresent across all human SARS-CoV-2 models, when present, its sequence is always highly conserved. It may be used as a potential target for the development of vaccines and therapeutic agents.
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