Fig. 2.

Three-dimensional structures of a bacterial lasso peptide (A), plant kalata B1 (B), human cathelicidin LL-37 (C), α-defensin 1 (HNP-1) (D), β-defensin-1 (HBD-1) (E), and rhesus theta defensin-1 (RTD-1) (F). Coordinates were obtained from the Protein Data Bank (PDB) (PDB IDs are 3NJW for the bacterial lasso BI-32169 [33]; 1JNU for membrane-bound kalata B1 [40]; 2K6O for membrane-bound LL-37 [78]; 3GNY for HNP-1 [90]; 1IJV for HBD-1 [133]; and 1HVZ for RTD-1 [134]. For clarity, only the three disulfide bonds in RTD-1 are displayed using space-filling model. A peptide bond forms between the N- and C-termini of kalata B1 and RTD-1. While the N-terminal amide of G1 and the carboxylic side chain of D9 form a macrolactam (pointed by an arrow in panel A), the C-terminal C19 forms a disulfide bond with C6. These structural scaffolds are remarkably stable to heat, chemicals, and proteases, making them ideal for peptide engineering through site-directed mutagenesis or peptide grafting (i.e. replacing an exposed loop of cyclotides with biologically active peptides) [135, 136]. For additional information on structural studies of natural AMPs, please refer to ref. [137].