Unique and exclusive peptide signatures directly identify intrinsically disordered proteins from sequences without structural information

Intrinsically disordered proteins are now widely accepted to play crucial roles in biological functions. Identification of signatures of intrinsic disorder is one of the key steps towards building a proper repertoire for their occurrence in proteomes. In this work, systematic computational synthesis of a library of all possible (3368400) dipeptides, tripeptides, tetrapeptides and pentapeptides using the natural 20 amino acids allowed us to identify 36 unique tetrapeptides present exclusively in intrinsically disordered proteins and absent in the complete primary sequence space of naturally occurring structured proteins. Further, out of more than 530000 known naturally occurring primary sequences without any structural information, 1349 sequences contain the above identified unique signatures of intrinsic disorder. These sequences, having cellular functions varying from housekeeping to metabolic to transport, more than double the number of the currently known intrinsically disordered proteins. On similar lines, we report that 26577 pentapeptide signatures exclusive to intrinsically disordered proteins, and absent in naturally occurring structured proteins, identify similar to 50% of more than half-a-million curated protein sequences without structural information to be intrinsically disordered. The results reported are a major leap forward in exploring functional manifestations of intrinsically disordered proteins. Communicated by Ramaswamy H. Sarma

Automated summary

This study identified unique signatures of intrinsic disorder by systematically synthesizing different peptide libraries, expanding the known intrinsically disordered proteins and providing a major advancement in exploring the functional manifestations of such proteins.