Enzymatic Control of the Conformational Landscape of Supramolecular Assembling Peptides
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. Biophysi...
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| Published in: | Angewandte Chemie International Edition Vol. 57; no. 35; pp. 11188 - 11192 |
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| Main Authors: | , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
25-07-2018
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| Online Access: | Get full text |
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| Summary: | 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, ultimately constituting the formation of cytocompatible hydrogel material.
Post-translational modification is a common mechanism to control protein conformational change and regulate function. Herein, we expand this principle to instruct the formation of supramolecular assemblies by controlling the conformational bias of self-assembling peptides. |
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| ISSN: | 1433-7851 1521-3773 |
| DOI: | 10.1002/anie.201803983 |