2YMK

Crystal structure of the hexameric anti-microbial peptide channel dermcidin

Summary for 2YMK

• Entry DOI: 10.2210/pdb2ymk/pdb
• Descriptor: DCD-1, ZINC ION (3 entities in total)
• Functional Keywords: antibiotic, anti-microbial peptide channel, membrane spanning peptide, human epidermal surface
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P81605
• Total number of polymer chains: 3
• Total formula weight: 14871.96

Authors

Zeth, K. (deposition date: 2012-10-09, release date: 2012-10-17, Last modification date: 2024-05-08)

Primary citation

Song, C.,Weichbrodt, C.,Salnikov, E.S.,Dynowski, M.,Forsberg, B.O.,Bechinger, B.,Steinem, C.,De Groot, B.L.,Zachariae, U.,Zeth, K.
Crystal Structure and Functional Mechanism of a Human Antimicrobial Membrane Channel.
Proc.Natl.Acad.Sci.USA, 110:4586-, 2013

PubMed Abstract: Multicellular organisms fight bacterial and fungal infections by producing peptide-derived broad-spectrum antibiotics. These host-defense peptides compromise the integrity of microbial cell membranes and thus evade pathways by which bacteria develop rapid antibiotic resistance. Although more than 1,700 host-defense peptides have been identified, the structural and mechanistic basis of their action remains speculative. This impedes the desired rational development of these agents into next-generation antibiotics. We present the X-ray crystal structure as well as solid-state NMR spectroscopy, electrophysiology, and MD simulations of human dermcidin in membranes that reveal the antibiotic mechanism of this major human antimicrobial, found to suppress Staphylococcus aureus growth on the epidermal surface. Dermcidin forms an architecture of high-conductance transmembrane channels, composed of zinc-connected trimers of antiparallel helix pairs. Molecular dynamics simulations elucidate the unusual membrane permeation pathway for ions and show adjustment of the pore to various membranes. Our study unravels the comprehensive mechanism for the membrane-disruptive action of this mammalian host-defense peptide at atomistic level. The results may form a foundation for the structure-based design of peptide antibiotics.

PubMed: 23426625
DOI: 10.1073/PNAS.1214739110

Experimental method

X-RAY DIFFRACTION (2.49 Å)