Lasso Peptide Unthreading: A Model System for Knotted Proteins

Lasso peptides are a class of protein-derived natural products with a curious threaded structure which endows the peptides with protease resistance and often thermostability. Lasso peptides have an array of therapeutically relevant activities ranging from antimicrobial function to receptor binding. Lasso peptides are also of interest because of their relatively simple entangled structure which can serve as a model system for larger knotted protein systems. In this talk I will present data on the kinetics and energetics of lasso peptide unthreading including experiments to precisely probe the unthreading mechanism.