Reassessing the exon–foldon correspondence using frustration analysis

Significance If globular protein domains consist of smaller units, folding and evolution would be facilitated. The fact that natural eukaryotic proteins are genetically partitioned in exons suggests that these may correspond with foldable regions. Here, we revisit the correspondence between exons and foldons, quasi-independent folding units, using concepts derived from energy landscape theory. We find that conserved exons are more foldable than other partitions of the primary structure. We describe that exon boundaries rarely interrupt the continuous secondary structures in the folded domain in most but not all of the protein families analyzed.