At group meeting a few weeks ago I presented this paper, “Landscape of Non-canonical Cysteines in Human VH Repertoire Revealed by Immunogenetic Analysis“, from Prabakaran and Chowdhury. The paper is an investigation of the frequency, location and patterns of cysteines contained in human antibody sequences. Cysteines are important amino acids found in proteins, including antibodies, which can form disulphide bonds with other cysteines due to the presence of their reactive sulfhydryl group in the side chain.

These disulphide bonds can stabilise protein structures, and we typically see a disulphide bond between a pair of cysteines in the human antibody framework region 1 and framework region 3 in viable antibody sequences. We know that cysteines are prevalent in the CDRH3 regions of antibodies in other species – particularly cow, shark, chicken, llama, duck-billed platypus and camel. In some of these species, the CDRH3 loop can be much longer than those typically found in human antibodies, and the cysteines can play a role in tethering these longer CDRH3s to other parts of the antibody structure for improved stability. By analysing higher numbers of human antibody sequences than had previously been studied, the authors of this paper determined that cysteines might be more common in the human CDRH3 region than previously thought, and might also be important in the binding region (the paratope) of the antibody. In investigating the patterns of cysteines present in CDRH3s, many varied motifs were discovered including some with up to eight cysteines! The implication for these findings is that perhaps we can use these motifs in our design of new therapeutic antibodies. 

If you think amino acids, such as cysteine, are interesting and would like to find out which amino acid truly represents you, here’s a quiz I found. Turns out I’m leucine – “You are very athletic. People depend on you for guidance and you also slow muscle atrophy.” Awesome.