Low Complexity Induces Structure in Protein Regions Predicted as Intrinsically Disordered

There is increasing evidence that many intrinsically disordered regions (IDRs) in proteins play key functional roles through interactions with other proteins or nucleic acids. These interactions often exhibit a context-dependent structural behavior. We hypothesize that low complexity regions (LCRs), often found within IDRs, could have a role in inducing local structure in IDRs. To test this, we predicted IDRs in the human proteome and analyzed their structures or those of homologous sequences in the Protein Data Bank (PDB). We then identified two types of simple LCRs within IDRs: regions with only one (polyX or homorepeats) or with only two types of amino acids (polyXY). We were able to assign structural information from the PDB more often to these LCRs than to the surrounding IDRs (polyX 61.8% > polyXY 50.5% > IDRs 39.7%). The most frequently observed polyX and polyXY within IDRs contained E (Glu) or G (Gly). Structural analyses of these sequences and of homologs indicate that polyEK regions induce helical conformations, while the other most frequent LCRs induce coil structures. Our work proposes bioinformatics methods to help in the study of the structural behavior of IDRs and provides a solid basis suggesting a structuring role of LCRs within them.

Automated summary

This study provides evidence that low complexity regions (LCRs) within intrinsically disordered regions (IDRs) of proteins can induce local structure. By predicting IDRs in the human proteome and analyzing structures in the Protein Data Bank (PDB), the researchers found that LCRs were more likely to have structural information assigned to them compared to surrounding IDRs. The most frequent LCRs containing E (Glu) or G (Gly) were found to induce helical or coil structures. These findings suggest a structuring role of LCRs within IDRs.