Cell-associating peptides (CAPs) are noted for their ability to penetrate cell membranes. Antimicrobial peptides, such as melittin, are able to form pores in bacterial cells leading to cell death. Protein transduction domains, such as TAT from the human immunodeficiency virus, are capable of translocating covalently- attached proteins and pharmaceutical molecules across cell membranes. Gaining full control over the functions of these peptides in vivo will lead to major advances in the fight against disease. Key components in the functioning of CAPs include membrane-induced folding and membrane insertion. Fluorescence energy transfer (FET) measurements can provide a full description of both of these events. Using FET experiments, the folding, insertion, and pore formation of melittin in lipid vesicles will be monitored. Melittin, which adopts a random coil structure in aqueous solution and a helical structure in lipid vesicles, provides a test case for monitoring CAP structure and function with FET measurements. Eventually these techniques will be used to study the form and function of other pertinent peptides, such as TAT. These measurements will significantly advance knowledge of protein-folding dynamics are crucial for controlling the actions of CAPs in vivo. ? ? ?
| Hartings, Matthew R; Kurnikov, Igor V; Dunn, Alexander R et al. (2010) Electron tunneling through sensitizer wires bound to proteins. Coord Chem Rev 254:248-253 |
| Hartings, Matthew R; Gray, Harry B; Winkler, Jay R (2008) Probing melittin helix-coil equilibria in solutions and vesicles. J Phys Chem B 112:3202-7 |
