Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Quiroz, Felipe García, Chilkoti, Ashutosh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
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
_version_ 1782396973346717696
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