Abstract
BackgroundIn order to characterize mammalian intrinsically disordered domains (IDDs) we examined the patterns in their amino acid abundance as well as overrepresented local sequence motifs. We considered IDDs from mouse proteins associated with innate immune responses as well as a set of generic human genes. These sets were compared with artificially generated random sequences with the same overall amino acid abundance and length distributions. IDDs were then clustered by amino acid abundance, and further analyzed in terms of co-occurrence of clusters with functionally characterized Pfam domains.ResultsOverall, IDDs were very different from randomly generated sequences. The deviation from random distributions was at least as great as that for ordered domains, for which the deviation can be rationalized in terms of strong evolutionary pressure for structure and function. The co-occurrence of certain Pfam domains with specific IDD clusters was found to be significant (p-value < 0.01). Local sequence motifs that were over-represented in the innate immune set consisted mostly of low complexity fragments, primarily characterized by amino acid repeats, and could not be assigned an obvious functional role.ConclusionsOur results suggest that IDDs are constrained within a narrow subset of possible sequences. This is most likely a result of biophysical restraints that have yet to be elucidated. More detailed examination of the functional relationship between the IDDs and associated Pfam domains is one possible avenue of investigation.
Highlights
In order to characterize mammalian intrinsically disordered domains (IDDs) we examined the patterns in their amino acid abundance as well as overrepresented local sequence motifs
The second is from a set of 1663 human proteins selected at random, excluding those in the Innate Immune Set
Similar IDD clusters share similar Pfam domains In order to assess whether similar IDD clusters are associated with similar ordered domains, we examined the co-occurrence of Pfam domains [13] in each pair of similar clusters as defined in the previous sub-section
Summary
In order to characterize mammalian intrinsically disordered domains (IDDs) we examined the patterns in their amino acid abundance as well as overrepresented local sequence motifs. We considered IDDs from mouse proteins associated with innate immune responses as well as a set of generic human genes. These sets were compared with artificially generated random sequences with the same overall amino acid abundance and length distributions. It has been shown that many IDDs become ordered upon binding other macromolecules [3], and that their binding modes can be diverse [4] with the length of the IDD modulating the binding affinity [5] This allows them to function as hubs in protein-protein interaction networks [6,7,8]. IDDs are generally filtered out when performing structure-based protein function prediction in order to focus attention on better-characterized ordered domains
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