In silico design of a novel hybrid epitope-based antigen harboring highly exposed immunogenic peptides of BamA, OmpA, and Omp34 against Acinetobacter baumannii

Article

Author: Khalesi, Bahman ; Mogharari, Zahra ; Reza Rahbar, Mohammad ; Hessami, Anahita ; Jahangiri, Abolfazl ; Khalili, Saeed ; Jamal Nassrullah, Othman ; Rahim, Fatemeh

Acinetobacter baumannii, is among the highest priority bacteria according to the WHO categorization which necessitate the exploration of alternative strategies such as vaccination. OmpA, BamA, and Omp34 are assigned as appropriate antigens to serve in vaccine development against this pathogen. Experimentally validated exposed epitopes of OmpA and Omp34 along with selected exposed epitopes predicted by an integrative in silico approach were represented by the barrel domain of BamA as a scaffold. Among the 8 external loops of BamA, 5 loops were replaced with selected loops of OmpA and Omp34. The designed antigen was analyzed regarding the physicochemical properties, antigenicity, epitope retrieval, topology, structure, and safety. BamA is a two-domain OMP with a 16-stranded barrel in which L4, L6, and L7 were the longest loops of BamA in order. The designed antigen consisted of 478 amino acids with antigen probability of 0.7793. The novel antigen was a 16-stranded barrel. No identical 8-meric peptides were found in the human proteome against the designed antigen sequence. The designed construct was safe regarding the allergenicity, toxicity, and human proteome reactivity. The designed antigen could develop higher protection against A. baumannii in comparison to either OmpA, BamA, or Omp34 alone.

01 Dec 2024·Molecular Biology Reports

Expression mechanisms of mir-486-5p and its host gene sANK1 in porcine muscle

Article

Author: Guo, Xiaoping ; Jiang, Qinyang ; Zhang, Mingyuan ; Ouyang, Yiqiang ; Lan, Ganqiu ; Guo, Yafen ; Liang, Jing

BACKGROUNDMiR-486-5p has been identified as a crucial regulator of the PI3K/AKT signalling pathway, which plays a significant role in skeletal muscle development. Its host gene, sANK1, is also essential for skeletal muscle development. However, the understanding of porcine miR-486-5p and sANK1 has been limited.METHODS AND RESULTSIn this study, PCR analyses revealed a positive correlation between the expression of miR-486-5p and sANK1 in the longissimus dorsi muscle of the Bama mini-pig and Landrace-pig, as well as during myoblast differentiation. Furthermore, the expression of miR-486-5p/sANK1 was higher in the Bama mini-pig compared to the Landrace-pig. There was a total of 18 single nucleotide polymorphisms (SNP) present in the sANK1 promoter region. Among these SNPs, 14 of them resulted in alterations in transcription factor binding sites (TFBs). Additionally, the promoter fluorescence assay demonstrated that the activity of the sANK1 promoter derived from the Bama mini-pig was significantly higher compared to Landrace-pig. It is worth noting that ten regulatory SNPs have the potential to influence the activity of the sANK1 promoter. A nuclear mutation A-G located at position - 401 (relative to the transcription start site) in the Bama mini-pig was identified, which creates a putative TFB motif for MyoD.CONCLUSIONSThe findings presented in this study offer fundamental molecular knowledge and expression patterns of miR-486-5p/sANK1, which can be valuable for gaining a deeper understanding of the gene's involvement in porcine skeletal muscle development, and meat quality.

15 Oct 2024·Proceedings of the National Academy of Sciences

Native β-barrel substrates pass through two shared intermediates during folding on the BAM complex

Article

Author: Kahne, Daniel E. ; Monfared, Tabasom H. ; Thomson, Benjamin D. ; Pan, Lydia ; dos Santos, Thiago M. A. ; Marquez, Melissa D.

The assembly of β-barrel proteins into membranes is mediated by the evolutionarily conserved β-barrel assembly machine (BAM) complex. In Escherichia coli , BAM folds numerous substrates which vary considerably in size and shape. How BAM is able to efficiently fold such a diverse array of β-barrel substrates is not clear. Here, we develop a disulfide crosslinking method to trap native substrates in vivo as they fold on BAM. By placing a cysteine within the luminal wall of the BamA barrel as well as in the substrate β-strands, we can compare the residence time of each substrate strand within the BamA lumen. We validated this method using two defective, slow-folding substrates. We used this method to characterize stable intermediates which occur during folding of two structurally different native substrates. Strikingly, these intermediates occur during identical stages of folding for both substrates: soon after folding has begun and just before folding is completed. We suggest that these intermediates arise due to barriers to folding that are common between β-barrel substrates, and that the BAM catalyst is able to fold so many different substrates because it addresses these common challenges.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

BamA

Basic Info

Related

Analysis