Self-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties

Area of Science:

• Synthetic biology
• Peptide self-assembly
• Nanomaterials science

Background:

• Coiled coils are key for synthetic biology and peptide-based nanostructures.
• Orthogonal peptides are typically used for complex assemblies, but negative design can limit stability.
• This work explores an alternative approach using non-orthogonal peptides.

Purpose of the Study:

• To design and characterize a set of de novo peptides that form parallel coiled coils.
• To investigate the self-sorting behavior of these peptides based on differential dimerization affinities.
• To demonstrate the potential of self-sorting for fabricating higher-order nanostructures.

Main Methods:

• De novo peptide design of four 28-residue sequences.
• Characterization of heterodimerization and dissociation constants (Kd).
• Thermal unfolding and fluorescence spectroscopy experiments.
• Molecular dynamics simulations to confirm self-sorting behavior.

Main Results:

• Four promiscuous peptides were designed that form parallel coiled coils.
• Peptides exhibit a wide range of dissociation constants, from micromolar to picomolar.
• Thermodynamic social self-sorting was observed, with high fidelity formation of the strongest and weakest heterodimers.
• Simulations confirmed the self-sorting phenomenon.

Conclusions:

• Differential binding affinities drive predictable self-sorting in designed peptide systems.
• This self-sorting strategy offers a viable route for assembling complex architectures.
• Exploiting self-sorting provides a powerful method for creating dynamic and tunable nanostructured materials.