Pore-forming proteins represent a class of proteins responsible for forming unregulated channels in cells. One common class of pore-forming proteins are antimicrobial peptides, many of which interact with, and disrupt, the bacterial cell membrane. Recently, evidence has suggested that amyloid proteins may also act as pore-forming proteins, disrupting cell membranes, although the mechanism by which this occurs is unclear. This research is focused on determining the relationship between the composition of a lipid membrane and the structure and action of pore-forming proteins. The interaction of these proteins were analyzed using hydrogen-deuterium exchange (HDX) and quadrupole time of flight mass spectrometry to gain information about the proteins’ conformational changes in the presence of model membranes. Proteins were studied in various membrane environments (e.g. anionic lipids, zwitterionic lipids, cholesterol, etc.) to understand how the lipid composition of a membrane may change the pore forming abilities of the protein. Our results indicate that the membrane composition does influence the conformation and interaction of the islet amyloid polypeptide (IAPP), an amyloid protein involved in type II diabetes. Our current studies with IAPP and with antimicrobial peptides are focused on gathering amino acid- specific data to understand which residues of the protein are buried (or are interacting with) different model membranes.

Effects of membrane composition on pore-forming polypeptides

253rd National Meeting (2017)

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