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Fig 1.

Study pipeline overview.

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Fig 2.

The current PDB structures related to a portion of the MBP sequence.

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Table 1.

The sequence information for Mycolicibacterium paratuberculosis, Epstein-Barr virus, and Homo sapiens, along with the corresponding protein names for each sequence (derived from previous studies) [12, 15].

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Table 2.

Protein sequence similarity and conserved amino acids, with bolded residues such as Arginine, Phenylalanine, Arginine, and Valine (observed in the cited study) [29].

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Table 3.

A summary of the data gathered from previous researches.

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Fig 3.

Alignment of BSH amino acid sequence from the bacteria and associated enzymes that participate in the butyric acid metabolic pathway.

The active site’s amino acids are highlighted in red, based on the structure of the BSH from C. perfringens.

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Fig 4.

The complex metabolic pathway involved in the production of polysaccharide A, a molecule with potential neuroprotective effects.

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Fig 5.

a) Amino acid sequence alignment of MBP with the HPV-B19 viral capsid protein. The first line displays the viral capsid amino acid sequence, the second line displays the MBP amino acid sequence, and the third line displays the scores associated with the amino acid alignment between the two sequences. In the amino acid alignment, the colors blue and red represent the gap and identity mode, respectively. Stars represent identity between all aligned amino acids. b) Position-specific scoring matrix for amino acid sequence alignment between HPV-B19 viral capsid protein and MBP protein.

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Fig 6.

a) Alignment of AAV-4 viral capsid protein with MBP amino acids sequence. The first line contains the amino acid sequence of the viral capsid coat, while the second line contains the amino acid sequence of the MBP. The third line depicts the consistency of each amino acid alignment from 0 to 10 (star). The similarity and identity of two amino acids are represented by points, with 0 representing the gap mode and a star indicating identity between all aligned amino acids. b) Scoring matrix for aligning amino acid sequences of AAV-4 viral capsid protein and MBP protein.

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Fig 7.

a) Alignment of tertiary structure between HPV-B19 capsid protein and MBP. b) Alignment of tertiary structure between AAV-4 capsid protein and MBP.

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Fig 8.

a) The 3D structure of the HPV-B19 capsid protein with red regions indicating the alignment of amino acids with a score greater than 8 b) The 3D structure of the AAV-4 capsid protein with blue regions indicating the alignment of amino acids with a score greater than 8 c) The alignment of both viral capsid proteins, with overlapping blue and red regions indicating amino acid alignment scores greater than 8. d) The overlapping regions of autoimmune encephalitis-associated amino acids in the HPV-B19 and AAV-4 viral capsid protein structures (GLY82, SER78, THR373, GLY374, SER377, GLN378, GLN379).

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Table 4.

BLAST Peptide of MBP sequence 230 to 236.

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Table 5.

The prediction scores for CD4+ T cell immunogenicity of the analyzed sequences using the CD4+ T cell prediction tool in the IEDB.

The scores for HLA-DRB1:15:01 allele is bolded and underlined as they are important in the association with MS.

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Table 6.

BLAST results of bacterial proteins.

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Fig 9.

a) Multiple alignments of MAP_0106, EBNA1, and MBP proteins. b) Multiple alignments of MAP_4027، BOLF1, and IRF5 proteins.

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Fig 10.

The multiple alignment results based on the two categories presented in Table 7.

a) shows the multiple alignment results of the first group of BLAST protein sequences (EBNA1, MAP 0106, MBP) b) shows the multiple alignment results of the second group of BLAST protein sequences (BOLF1, IRF5, MAP4027).

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Table 7.

The BLAST results for two categories of protein sequences: 1.

MAP 0106, EBNA1, and MBP and 2. MAP 4027, BOLF1, and IRF5.

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Fig 11.

Diagram of the sequences of epitope antigens obtained from Table 7.

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Table 8.

The sequences of the antigen as an epitope structure.

Each amino acid from the sequences has a corresponding score in the epitope structure, which is shown in Fig 11. Amino acids with scores higher than the threshold (0.5) in this prediction tool are bolded.

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Table 8 Expand

Fig 12.

Alignment of epsilon toxin of Clostridium perfringens and ORF3 protein of Nora virus.

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Fig 13.

Sequence analysis of epsilon toxin and ORF3 proteins as an antigen epitope.

The diagram in this figure shows the position of amino acids in each sequence on the horizontal axis and the score of each amino acid on the vertical axis. Also, the amino acids are shown separately, in which their score of them are higher than the threshold, and they were bolded (Table 9).

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Table 9.

Antigen epitopes derived from Nora virus and Clostridium perfringens-related sequences.

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Fig 14.

a) Sequence alignment of MBP 246–256 with spike glycoprotein 349–359. b) Sequence alignment of 68 to 76 MOG with 28 to 36 spike glycoproteins.

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Fig 15.

a) Sequence alignment of MBP 246–256 with main protease 5487–5497. b) Sequence alignment of 68 to 76 MOG with 1975 to 1983 main protease.

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Fig 16.

a) Alignment of C. perfringens BSH enzyme sequences (227–237) and MBP (from 246 to 256). b) Protected points in the alignment of three bacterial sequences of C. perfringens, B. longum, L. plantarum, and MBP.

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Fig 17.

a) Alignment of human and mouse MOG with BSH protein from C. perfringens. b) Multiple alignments of MOG with the BSH proteins from C. perfringens, B. longum, and L. plantarum.

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Fig 18.

3D structure alignment and motif analysis of B. Longum (purple and red) and C. Perfringens (yellow and green) BSH proteins with MOG sequence.

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Fig 19.

Relationship between MOG and the Wzy enzyme.

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Fig 20.

MOG (mouse and human) alignment with the bacterial enzyme WcfQ.

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