How to Tie a Peptide Knot

Lasso peptides are short peptides (~20 aa) produced by bacteria that have a unique knotted topology in which the N-terminus of the peptide forms an isopeptide bond with a glutamic acid or aspartic acid sidechain.  The C-terminal "tail" of the peptide is fed through the resulting macrocycle resulting in the characteristic lasso structure.  Lasso peptides have tremendous resistance to chemical and thermal denaturation and exhibit resistance to most proteases making this scaffold attractive for therapeutic and diagnostic uses.  This talk will focus on work in my group exploring the engineering potential of the lasso peptide framework as well basic studies aimed at understanding the folding of lasso peptides and elucidating the biosynthetic pathways bacteria use to make these peptides.