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

By Conan K. Wang, Gordon J. King, Anne C. Conibear, Mariana C. Ramos, Stephanie Chaousis, Sónia Troeira Henriques, David J. Craik

July 28, 2017

  • Year

  • Technique

  • Industry

Title

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

Author

Conan K. Wang, Gordon J. King, Anne C. Conibear, Mariana C. Ramos, Stephanie Chaousis, Sónia Troeira Henriques, David J. Craik

Year

2016

Journal

JACS

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.

Full Article

http://pubs.acs.org/doi/abs/10.1021/jacs.6b02575

Instrument

J-810

Keywords

Circular dichroism, Stereochemistry, Biochemistry