Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

By Felipe Garcia Quiroz, A. Chilkoti. Nature Materials, 2015

390 citations recorded by the source corpus.

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.

Subfields: Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1f99f449ede8f37e19538c68477fb88228ce0c84

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Citations in the corpus

Sequence determinants of protein phase behavior from a coarse-grained model (2017, background): “The phase behavior at the lower critical solution 503 temperature, which is observed in some disordered peptides experimentally [31], cannot 504 be captured, either.”
Pi-Pi contacts are an overlooked protein feature relevant to phase separation (2018, methodology): “The Phe- Gly repeats in FG nucleoporins similarly indicate pi-pi interactions, but the lack of aromatics in elas- tins and designed phase-separating sequences (Quiroz and Chilkoti, 2015) seems to suggest that they are not essential.”
Liquid phase condensation in cell physiology and disease (2017, background): “Although typical condensed phases dissolve upon increasing temperature, which is associated with an upper critical solution temperature (UCST), hydrophobic interactions can manifest in lower critical solution temperature (LCST)—phase separation upon increasing temperature, as observed in vitro with ”