Nature and mimetics: The PPII secondary structure in protein functionality and assembly of higher order structures

The polyproline II helix is more common as a secondary structure than previously thought. Its significance extends to mediating various protein-protein interactions, both structurally and functionally, in natural systems. This structure is associated with the formation of supramolecular assemblies, which have been investigated for biomimetic applications. We present three examples of utilizing polyproline II helices: structurally in collagen and biomolecular condensates, and functionally in the creation of hyperactive antifreeze proteins. Additionally, we thoroughly discuss the detection limits of these helices using a range of current biophysical methods and artificial intelligence-based models.