TY - JOUR
T1 - Plectasin, a Fungal Defensin, Targets the Bacterial Cell Wall Precursor Lipid II
AU - Schneider, Tanja
AU - Kruse, Thomas
AU - Wimmer, Reinhard
AU - Wiedemann, Imke
AU - Sass, Vera
AU - Pag, Ulrike
AU - Jansen, Andrea
AU - Nielsen, Allan K.
AU - Mygind, Per H.
AU - Raventos, Dorotea S.
AU - Neve, Søren
AU - Ravn, Birthe
AU - Bonvin, Alexandre M.J.J.
AU - De Maria, Leonardo
AU - Andersen, Anders S.
AU - Gammelgaard, Lora K.
AU - Sahl, Hans-Georg
AU - Kristensen, Hans-Henrik
PY - 2010/5/28
Y1 - 2010/5/28
N2 - Host defense peptides such as defensins are components of innate immunity and have retained antibiotic activity throughout evolution. Their activity is thought to be due to amphipathic structures, which enable binding and disruption of microbial cytoplasmic membranes. Contrary to this, we show that plectasin, a fungal defensin, acts by directly binding the bacterial cell-wall precursor Lipid II. A wide range of genetic and biochemical approaches identify cell-wall biosynthesis as the pathway targeted by plectasin. In vitro assays for cell-wall synthesis identified Lipid II as the specific cellular target. Consistently, binding studies confirmed the formation of an equimolar stoichiometric complex between Lipid II and plectasin. Furthermore, key residues in plectasin involved in complex formation were identified using nuclear magnetic resonance spectroscopy and computational modeling.
AB - Host defense peptides such as defensins are components of innate immunity and have retained antibiotic activity throughout evolution. Their activity is thought to be due to amphipathic structures, which enable binding and disruption of microbial cytoplasmic membranes. Contrary to this, we show that plectasin, a fungal defensin, acts by directly binding the bacterial cell-wall precursor Lipid II. A wide range of genetic and biochemical approaches identify cell-wall biosynthesis as the pathway targeted by plectasin. In vitro assays for cell-wall synthesis identified Lipid II as the specific cellular target. Consistently, binding studies confirmed the formation of an equimolar stoichiometric complex between Lipid II and plectasin. Furthermore, key residues in plectasin involved in complex formation were identified using nuclear magnetic resonance spectroscopy and computational modeling.
U2 - 10.1126/science.1185723
DO - 10.1126/science.1185723
M3 - Journal article
SN - 0036-8075
VL - 328
SP - 1168
EP - 1172
JO - Science
JF - Science
IS - 5982
ER -