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Fluorescent Leakage Assay to Investigate Membrane Destabilization by Cell-Penetrating Peptide
Published on: December 19, 2020
The effects of flanking sequences in the interaction of polyglutamine peptides with a membrane bilayer
Anu Nagarajan1, Sudi Jawahery, Silvina Matysiak
1Fischell Department of Bioengineering, University of Maryland , College Park, Maryland 20742, United States.
Abstract:
Huntington's disease (HD) is caused by the presence of an extended polyglutamine (polyQ) region at the N-terminus of the huntingtin (htt) protein. The presence of flanking sequences adjacent to the polyQ region has been reported to modulate the effects of potentially toxic protein-membrane interactions. In this study, we consider four peptide systems with various combinations of flanking sequences (KKQ35KK, KKQ35P11KK, N17Q35KK, N17Q35P11KK) and use atomistic molecular dynamics simulations to study the interactions with a DOPC lipid bilayer. We observe significant membrane thinning, disorderliness of lipid molecules, and compensation effects between the top and the bottom leaflets of the bilayer depending on the presence of particular flanking sequences. Overall, we find that the presence of the N-17 flanking sequence is crucial for membrane interactions. Polyproline decreases the interaction with the membrane in the absence of N-17, but enhances it when present along N-17.
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