Enzymatic Control of the Conformational Landscape of Self-Assembling Peptides.
Angew Chem Int Ed Engl
; 57(35): 11188-11192, 2018 08 27.
Article
em En
| MEDLINE
| ID: mdl-29969177
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Materiais Biocompatíveis
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Hidrogéis
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article