Mirror Images of Antimicrobial Peptides Provide Reflections on Their Functions and Amyloidogenic Properties

Abstract

Enantiomeric forms of BTD-2, PG-1, and PM-1 were synthesized to delineate the structure and function of these β-sheet antimicrobial peptides. Activity and lipid-binding assays confirm that these peptides act via a receptor-independent mechanism involving membrane interaction. The racemic crystal structure of BTD-2 solved at 1.45 Å revealed a novel oligomeric form of β-sheet antimicrobial peptides within the unit cell: an antiparallel trimer, which we suggest might be related to its membrane-active form. The BTD-2 oligomer extends into a larger supramolecular state that spans the crystal lattice, featuring a steric-zipper motif that is common in structures of amyloid-forming peptides. The supramolecular structure of BTD-2 thus represents a new mode of fibril-like assembly not previously observed for antimicrobial peptides, providing structural evidence linking antimicrobial and amyloid peptides.

Mammalian antimicrobial peptide protegrin‐4 self assembles and forms amyloid‐like aggregates: Assessment of its functional relevance

“…AMPs have been a prominent candidate for the development of new peptide‐based antimicrobials due to their various positive attributes . Reports on the self‐assembly properties of AMPs and antimicrobial activity of some amyloid structures provide a hint about the relationship between these two classes of peptides . It has been reported that diphenylalanine self‐assemblies have antibacterial activity and selective toxicity towards bacterial cells .…”

“…3 Reports on the self-assembly properties of AMPs and antimicrobial activity of some amyloid structures provide a hint about the relationship between these two classes of peptides. 30,62 It has been reported that diphenylalanine self-assemblies have antibacterial activity and selective toxicity towards bacterial cells. 63 Therefore, in this study, Conventionally, amyloids have always been associated with disease conditions and toxic potentials.…”

Transmembrane Pore Structures of β-Hairpin Antimicrobial Peptides by All-Atom Simulations

“…The mixed topology was inspired by a recent crystallization study of a θ-defensin AMP, which found a mixed-topology trimer wherein one dimer had NCNC parallel topology and the other NCCN antiparallel topology (Fig. 1) 50 .…”

On the Role of Chirality in Guiding the Self‐Assembly of Peptides

“…There is evidence that homochirality is required to create biopolymers with af unction. [9,10] Peptide molecules that can mimic large proteins are biologically active building blocks for the production of self-assembled nanostructures. [8] This suggests that homochirality plays ac ritical role for the structure and function of such systems,i ncluding sustaining self-replications cycles,however, chirality guided interactions between peptide molecules in the context of functionality are rarely explored.…”