NMR structure and localization of the host defense antimicrobial peptide thanatin in zwitterionic dodecylphosphocholine micelle: Implications in antimicrobial activity

Thanatin: An Emerging Host Defense Antimicrobial Peptide with Multiple Modes of Action

“…The 3-D structure and orientation of thanatin have recently been reported in zwitterionic DPC micelles (Figure 2D) [26]. In DPC, thanatin assumed a disulfide-stabilized monomeric β-hairpin structure with a flexible N-terminal segment, akin to the structure determined in free solution [26,27]. Several other studies of AMPs also demarcated the striking differences between structures in LPS and in detergent micelles.…”

“…Residues R13, R14, and K17, in the β-turn of the β-hairpin, are located on the same side of K3 and K4 residues at the N-terminus, yielding large cationic surfaces at the two opposite ends of the structure (Figure 2C). The 3-D structure and orientation of thanatin have recently been reported in zwitterionic DPC micelles (Figure 2D) [26]. In DPC, thanatin assumed a disulfide-stabilized monomeric β-hairpin structure with a flexible N-terminal segment, akin to the structure determined in free solution [26,27].…”

“…Brevinins have been described to adopt helical conformations in membrane-mimetic environments [25]. On the contrary, thanatin is characterized by a β-hairpin structure in its C-terminal region, retained in both free and detergent solutions, which is considered integral for its activity [26,27]. Remarkably, thanatin is a uniquely multifaceted peptide bestowed with more than one distinct mechanism of antimicrobial activity that is opposed to the commonly observed membrane disruption ability of several cationic AMPs.…”

Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides

“…In LPS outer membrane, thanatin adopts a dimeric structure whereby residues of the N-terminal β-strand of each sub-unit deduced to be engaged in interfacial interactions (Figure 4A-C). Note that thanatin forms monomeric β-hairpin structures in free solution and also in zwitterionic DPC micelle [87,91]. Therefore, the dimeric structure of thanatin can be considered as a specific consequence of binding with negatively charged LPS outer membrane (Figure 4D).…”

“…Sci. 2022, 23, x 8 of 24 zwitterionic DPC micelle [87,91]. Therefore, the dimeric structure of thanatin can be considered as a specific consequence of binding with negatively charged LPS outer membrane (Figure 4D).…”