Engineering Synthetic Electron Transfer Chains from Metallopeptide Membranes

Area of Science:

• Biochemistry
• Bioinorganic Chemistry
• Materials Science

Background:

• Copper cupredoxins are vital electron transfer chain (ETC) proteins.
• Understanding their energetic and geometric features is key to designing artificial electron transfer systems.
• Synthetic scaffolds can mimic biological electron transfer functionalities.

Purpose of the Study:

• To create a synthetic peptide-copper assembly that mimics the function of cupredoxins in electron transfer.
• To investigate the structural and electronic properties of copper sites within a self-assembled peptide bilayer.
• To explore the mechanism of electron transfer in this artificial system.

Main Methods:

• Templating a synthetic nonapeptide (HHQALVFFA-NH2) with copper ions to form cross-β bilayer assemblies.
• Utilizing electron spin echo envelope modulation and X-ray absorption spectroscopies to characterize copper sites.
• Employing restrained molecular dynamics to model the peptide bilayer architecture.
• Conducting cyclic voltammetry to study electron transfer mechanisms.

Main Results:

• The synthetic assemblies exhibit copper sites with blue-shifted electronic transitions and high reduction potentials, akin to plastocyanin.
• Square planar Cu(II) sites coordinated by a single histidine ligand were identified.
• Molecular dynamics simulations confirmed metal ion coordination stabilizing the peptide interface.
• Cyclic voltammetry revealed a charge-hopping mechanism for electron transfer between copper centers spaced 10-12 Å apart.

Conclusions:

• The metal-templated peptide scaffold successfully mimics cupredoxin functionality and electron shuttle capabilities.
• This system represents a novel peptide membrane-localized electron transport chain.
• The high reduction potential is attributed to factors beyond simple geometric distortion (entasis).