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Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers.

Publication ,  Journal Article
Ruff, KM; Roberts, S; Chilkoti, A; Pappu, RV
Published in: Journal of molecular biology
November 2018

Proteins and synthetic polymers can undergo phase transitions in response to changes to intensive solution parameters such as temperature, proton chemical potentials (pH), and hydrostatic pressure. For proteins and protein-based polymers, the information required for stimulus-responsive phase transitions is encoded in their amino acid sequence. Here, we review some of the key physical principles that govern the phase transitions of archetypal intrinsically disordered protein polymers (IDPPs). These are disordered proteins with repetitive amino acid sequences. Advances in recombinant technologies have enabled the design and synthesis of protein sequences of a variety of sequence complexities and lengths. We summarize insights that have been gleaned from the design and characterization of IDPPs that undergo thermo-responsive phase transitions and build on these insights to present a general framework for IDPPs with pH and pressure responsive phase behavior. In doing so, we connect the stimulus-responsive phase behavior of IDPPs with repetitive sequences to the coil-to-globule transitions that these sequences undergo at the single-chain level in response to changes in stimuli. The proposed framework and ongoing studies of stimulus-responsive phase behavior of designed IDPPs have direct implications in bioengineering, where designing sequences with bespoke material properties broadens the spectrum of applications, and in biology and medicine for understanding the sequence-specific driving forces for the formation of protein-based membraneless organelles as well as biological matrices that act as scaffolds for cells and mediators of cell-to-cell communication.

Duke Scholars

Published In

Journal of molecular biology

DOI

EISSN

1089-8638

ISSN

0022-2836

Publication Date

November 2018

Volume

430

Issue

23

Start / End Page

4619 / 4635

Related Subject Headings

  • Temperature
  • Repetitive Sequences, Amino Acid
  • Protein Conformation
  • Polymers
  • Phase Transition
  • Organelles
  • Models, Molecular
  • Intrinsically Disordered Proteins
  • Hydrostatic Pressure
  • Hydrogen-Ion Concentration
 

Citation

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Ruff, K. M., Roberts, S., Chilkoti, A., & Pappu, R. V. (2018). Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers. Journal of Molecular Biology, 430(23), 4619–4635. https://doi.org/10.1016/j.jmb.2018.06.031
Ruff, Kiersten M., Stefan Roberts, Ashutosh Chilkoti, and Rohit V. Pappu. “Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers.Journal of Molecular Biology 430, no. 23 (November 2018): 4619–35. https://doi.org/10.1016/j.jmb.2018.06.031.
Ruff KM, Roberts S, Chilkoti A, Pappu RV. Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers. Journal of molecular biology. 2018 Nov;430(23):4619–35.
Ruff, Kiersten M., et al. “Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers.Journal of Molecular Biology, vol. 430, no. 23, Nov. 2018, pp. 4619–35. Epmc, doi:10.1016/j.jmb.2018.06.031.
Ruff KM, Roberts S, Chilkoti A, Pappu RV. Advances in Understanding Stimulus-Responsive Phase Behavior of Intrinsically Disordered Protein Polymers. Journal of molecular biology. 2018 Nov;430(23):4619–4635.
Journal cover image

Published In

Journal of molecular biology

DOI

EISSN

1089-8638

ISSN

0022-2836

Publication Date

November 2018

Volume

430

Issue

23

Start / End Page

4619 / 4635

Related Subject Headings

  • Temperature
  • Repetitive Sequences, Amino Acid
  • Protein Conformation
  • Polymers
  • Phase Transition
  • Organelles
  • Models, Molecular
  • Intrinsically Disordered Proteins
  • Hydrostatic Pressure
  • Hydrogen-Ion Concentration