Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

• Published in: Nature materials 2015-11, Vol.14 (11), p.1164-1171
• Main Authors: Quiroz, Felipe García, Chilkoti, Ashutosh
• Format: Article
• Language: English
• Subjects: 639/166/985; 639/301/357/341; 639/301/54/989; 639/301/923/1028; Amino acids; Animals; Biomaterials; Condensed Matter Physics; Design engineering; Heuristic; Humans; Materials Science; Mutation; Nanotechnology; Optical and Electronic Materials; Phase transformations; Physiology; Polymers; Proteins; Proteome - chemistry; Proteome - genetics; Repetitive Sequences, Amino Acid - genetics; Residues; Self assembly; Sequence Analysis, Protein - methods
• ISSN: 1476-1122; 1476-4660
• DOI: 10.1038/nmat4418

Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level. Intrinsically disordered protein polymers can be designed to encode tunable lower or upper critical solution temperatures in physiological solutions.