Extremophilic behavior of catalytic amyloids sustained by backbone structuring

Area of Science:

• Biochemistry
• Materials Science
• Biophysics

Background:

• Enzyme function depends on precise chemical arrangements stabilized by protein backbone hydrogen bonds.
• Amyloids, known for self-associative hydrogen bonds, can mimic enzyme activity and stability.
• Previous studies showed some stability, but extreme properties and molecular basis remained unclear.

Purpose of the Study:

• To define the extremophilic properties of catalytic amyloids.
• To elucidate the molecular mechanisms behind their extreme activity and stability.
• To explore their potential for synthetic applications.

Main Methods:

• Investigated catalytic amyloid activity across a range of temperatures and solvents.
• Utilized in situ non-linear 2D infrared spectroscopy (2DIR) to analyze backbone vibrational states.
• Employed molecular modeling to understand structural changes and bonding dynamics.

Main Results:

• Catalytic amyloid activity persists and optimizes at high temperatures (81 °C), showing 30-fold increase.
• Amyloids retain structure and activity above 100 °C and in co-solvents.
• 2DIR revealed reorganized backbone hydrogen bonds and an emergent vibrational mode at 1612 cm⁻¹.
• Molecular modeling confirmed stabilization through restructured hydrogen bonds in organic solvents.

Conclusions:

• Catalytic amyloids possess extreme stability and activity, surpassing thermophilic enzymes.
• Restructuring of backbone hydrogen bonds is key to maintaining function in harsh environments.
• These properties make amyloids promising for synthetic applications requiring robust biocatalysts.