PEPTIDE ANTIBIOTICS

Baylor College Of Medicine, Houston TX

Investigators

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Magainin is a peptide antibiotic that interacts directly with the lipid membrane in the target cell. The mode of action for magainin and related peptides is formation of large nonselective pores in the membrane leading to cell lysis. A number of methods, like Circular Dichroism, Solid State NMR, Raman Scattering, Neutron Scattering, etc., have been used to infer this mode of action. However, none of those methods has directly visualized the structure of an individual pore, and some puzzling inconsistencies exist in the current models. Here we present a new method for studying peptide/lipid interactions, which employs Cryo-EM to image Magainin-induced pores in phospholipid vesicles. Since the size of the putative pores is quite small for direct observation of individual pores, we are also analyzing the cryo-EM data in a scattering context. That is, performing 'virtual'electron scattering experiments through analysis of the power spectra of selected vesicles. While we hope to directly image individual pores, as a first step this permits observation of the effects of Magainin in bulk specimens, and relating the cryoEM results to previous X-ray and neutron scattering experiments.