Intrinsically Disordered Peptide Nanofibers from a Structured Motif Within Proteins

Area of Science:

• Biomaterials Science
• Protein Engineering
• Nanotechnology

Background:

• Intrinsically disordered regions (IDRs) are crucial for protein function and signaling via higher-order assemblies.
• The assembly properties and functions of intrinsically disordered peptides (IDPs) remain underexplored.
• Developing strategies for engineering IDP assemblies is essential for novel biomaterial design.

Purpose of the Study:

• To develop a facile strategy for engineering intrinsically disordered peptide (IDP) assemblies.
• To investigate the formation and properties of self-assembled nanofibers derived from a modified peptide.
• To explore the potential of these nanofibers as cell-compatible biomaterials.

Main Methods:

• Conjugation of a structured phosphorylation site motif to a self-assembling tripeptide via a glycine linker.
• Generation of a phosphorylated octapeptide and subsequent dephosphorylation to induce hydrogel formation.
• Cryo-electron microscopy (cryo-EM) for structural analysis of the self-assembled nanofibers.

Main Results:

• Successfully engineered self-assembling nanofibers with intrinsic disorder from a modified peptide.
• The resulting phosphooctapeptide is cell-compatible and forms a hydrogel upon dephosphorylation.
• Cryo-EM revealed helical arrangements within the nanofibers, with disordered peripheries.
• Hydrogels demonstrated reduced protein adsorption correlating with increased peptide concentration.

Conclusions:

• This study presents the first instance of a structured random coil transitioning to an intrinsically disordered state within self-assembled peptide nanofibers.
• The findings expand the sequence repertoire for IDPs and offer insights into engineering disordered peptide nanofibers.
• The developed nanofibers show promise for creating cell-compatible biomaterials with tunable properties.