Summary

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BID is crucial for cellular functions due its significant role in the apoptotic pathway, and is implicated in many pathologies. In humans, four BID isoforms have been identified and are present in at least 38 other species. We have highlighted the importance of the BH3 domain in human isoforms 1, 2, and all of the orthologues presented on this site. The BH3-B domain is  present in all species except in human isoform 2 and the zebrafish homolog, which emphasises its evolutionary importance. Additionally, BID has a similar structure to 1XDT, the diphtheria toxin. However, their similarity is likely to be of convergent origin due to the lack of conservation between the sequences but has similarity in function.

To attain these findings, BLASTp and MSA analysis in tandem were used to infer functional and evolutionary relationships between sequences and identify member of gene families. MSA allowed us to compare sequences of proteins in order to analyse protein structure, predict protein function, and infer phylogenetic relationships. The primary sequences in FASTA format were used to generate the MSA in Clustal Omega. MSA analysis comparing orthologues confirmed that the BID domain was conserved. Furthermore, MSA analysis comparing human isoforms highlighted how their differences in sequences lead to differences in function. The tertiary structure of BID was visualised using Pymol and the two hydrophobic helices were found to be visually consistent with the function to our knowledge. The hydrophobic region is key as it is the part of the protein that embeds in the outer mitochondrial membrane, eventually leading to the permeabilisation of the membrane, triggering cell death. A thorough structural and functional understanding of BID is of great importance in medical research for developing effective treatment against pathologies involving BID mutations, including cancer.

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By: TM, SA, MW, HG, WR, TK