Enzymatic Control of the Conformational Landscape of Self-Assembling Peptides

Junfeng Shi, Galit Fichman, Joel P. Schneider*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Post-translational modification is a common mechanism to affect conformational change in proteins, which in turn, regulates function. Herein, this principle is expanded to instruct the formation of supramolecular assemblies by controlling the conformational bias of self-assembling peptides. Biophysical and mechanical studies show that an engineered phosphorylation/dephosphorylation couple can affectively modulate the folding of amphiphilic peptides into a conformation necessary for the formation of well-defined fibrillar networks. Negative design principles based on the incompatibility of hosting residue side-chain point charge within hydrophobic environments proved key to inhibiting the peptide's ability to adopt its low energy fold in the assembled state. Dephosphorylation relieves this restriction, lowers the energy barrier between unfolded and folded peptide, and allows the formation of self-assembled fibrils that contain the folded conformer, thus ultimately enabling the formation of a cytocompatible hydrogel material.

Original languageAmerican English
Pages (from-to)11188-11192
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number35
DOIs
StatePublished - 27 Aug 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • enzymes
  • phosphorylation
  • protein folding
  • self-assembly
  • supramolecular hydrogel

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