A conformational two-state peptide model system containing an ultrafast but soft light switch

Area of Science:

• Biochemistry
• Molecular Biology
• Photochemistry

Background:

• Protein disulfide isomerase (PDI) plays a crucial role in protein folding and cellular signaling.
• Allosteric conformational rearrangements are fundamental to biological processes.
• Azobenzene chromophores are known for their light-induced isomerization properties.

Purpose of the Study:

• To construct a model system that mimics cellular signaling events through light-induced conformational changes.
• To investigate the relationship between azobenzene isomerization and peptide structure.
• To explore the dynamics of photoisomerization within a cyclic peptide.

Main Methods:

• Construction of a cyclic peptide incorporating an azobenzene chromophore and the PDI active-site sequence.
• Nuclear Magnetic Resonance (NMR) spectroscopy to analyze peptide structures.
• Ultrafast UV/Vis spectroscopy to study the dynamics of azobenzene isomerization.

Main Results:

• The trans-azo and cis-azo isomers of the cyclic PDI peptide exhibit distinct, well-defined structures when cross-linked by a disulfide bridge.
• The absence of the disulfide bridge leads to conformationally more variable structural ensembles that differ between isomers.
• Azobenzene isomerization in cyclic peptides is rapid, with altered ballistic and diffusive pathway amplitudes.
• Most absorbed photon energy is dissipated to the solvent during isomerization, resulting in weakly driven conformational rearrangement.

Conclusions:

• The developed model effectively demonstrates light-induced allosteric conformational rearrangements.
• The study highlights the influence of disulfide bridges on peptide structure and isomer-specific conformations.
• The findings suggest that photoisomerization in such systems can be described as biased diffusion, akin to natural processes.