Epitope Mapping Using Homolog-Scanning Mutagenesis

With the advance of whole genome sequencing for an increasing number of organisms, it becomes clear that many proteins exist in multiple forms whose overall structures are similar despite subtle sequence and functional differences. Although the biological significance may not be known for some homologs in a gene family, they nevertheless provide a useful tool for mapping of functional domains or sites involved in inter-molecular interactions. This is also true for epitope mapping. Determination of antibody-binding sites using serial chimeric proteins of different homologs, a technique termed homolog-scanning mutagenesis (HSM), has proven to be especially useful in mapping conformational epitopes.