원문정보
초록
영어
Glycolipids offer recognition sites of a variety of proteins such as antibodies and microbial toxins, thereby playing physiological and pathological roles on cell membrane surfaces.Therefore, these glycolipid-protein interaction systems could be potential therapeutic targets for various diseases, including bacterial infections and neurodegenerative disorders [1]. To elucidate the underlying mechanisms of molecular recognition between glycolipids and proteins, we investigatedthe interaction between sarcotoxin IA and lipid Aas a model system to characterize conformational transitions and intermolecular interactions of the membrane-binding peptides promoted on glycolipids. Lipid A is a major component of the outer membrane of Gram-negative bacteria and can be a recognition target in the innate immune system. This molecule can also serve as targets of sarcotoxin IA, which is a 39-residue cecropin-type antibacterial peptide from Sarcophaga peregrina. In order to obtain structural information at atomic level, we expressed sarcotoxin IA peptides in Escherichia coli to achieve 13C- and15N-labeling for detailed NMR analyses. We observed NMR spectral changes of sarcotoxin IA upon interacting with lipid A, which was embeded in micelles composed of dodecylphosphocholine. Our spectroscopic data revealed that the N-terminal segment of sarcotoxin IA was converted from random- coil to an amphiphilic α-helix upon specific binging to lipid A. By inspecting chemical shift perturbation data, we successfully identified key lysine residues involved in interaction with lipid A and consequent antibacterial activity.