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Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers
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 protei...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618764/ https://www.ncbi.nlm.nih.gov/pubmed/26390327 http://dx.doi.org/10.1038/nmat4418 |
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author | Quiroz, Felipe García Chilkoti, Ashutosh |
author_facet | Quiroz, Felipe García Chilkoti, Ashutosh |
author_sort | Quiroz, Felipe García |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4618764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-46187642016-05-01 Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers Quiroz, Felipe García Chilkoti, Ashutosh Nat Mater Article 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. 2015-09-21 2015-11 /pmc/articles/PMC4618764/ /pubmed/26390327 http://dx.doi.org/10.1038/nmat4418 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Quiroz, Felipe García Chilkoti, Ashutosh Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers |
title | Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers |
title_full | Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers |
title_fullStr | Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers |
title_full_unstemmed | Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers |
title_short | Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers |
title_sort | sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618764/ https://www.ncbi.nlm.nih.gov/pubmed/26390327 http://dx.doi.org/10.1038/nmat4418 |
work_keys_str_mv | AT quirozfelipegarcia sequenceheuristicstoencodephasebehaviourinintrinsicallydisorderedproteinpolymers AT chilkotiashutosh sequenceheuristicstoencodephasebehaviourinintrinsicallydisorderedproteinpolymers |