2YMK

Crystal structure of the hexameric anti-microbial peptide channel dermcidin

2YMK の概要

• エントリーDOI: 10.2210/pdb2ymk/pdb
• 分子名称: DCD-1, ZINC ION (3 entities in total)
• 機能のキーワード: antibiotic, anti-microbial peptide channel, membrane spanning peptide, human epidermal surface
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: P81605
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 14871.96

構造登録者

Zeth, K. (登録日: 2012-10-09, 公開日: 2012-10-17, 最終更新日: 2024-05-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.49 Å)