Mechanism of structural transition between α-helix and β-sheet of penetrating peptides in lipid membrane

Wei-Chin Hung^1*, Chih-Chin Chiu¹

¹Department of physics, R.O.C military Academy, Kaohsiung, Taiwan

* Presenter:Wei-Chin Hung, email:hung.wc0602@msa.hinet.net

Penetratin is a cell-penetrating peptide whose state has been revealed by the literature to be related to the Peptide-to-Lipid (P/L) ratio, and when the concentration of Penetratin increases, its structure changes from α-helix to β-sheet. It is generally believed that the transition from α-state to β-state structure is an irreversible process, and studies have shown that beta formation is related to Alzheimer's symptoms. Therefore, studying the state change of Penetratin will help to understand the aggregation process of β-amyloid, and understanding the mechanism of the transition between α-state and β-state will be an important research topic, but this mechanism has not been clearly understood. We used circular dichroism to observe the acid-base environment from pH 2 to 11, controlled the SUV solution at 6.36 mM, and measured the range of P/L=1/20 to 1/100 to study the pH effect. In addition, we controlled P/L at 1/20 and measured the spectrum of SUV solution diluted from 318 μM to 42.4μM to check the concentration effect of SUV solution. The results of the pH effect show that a high concentration of Penetratin and a low pH solution contribute to β-state formation. However, the pH value only has an obvious effect under pH<3 conditions. The results of the SUV concentration effect show that when the solution is diluted low enough, the original β-state can be converted back to the α-state. It can be inferred from the above results, that the state of Penetratin in the lipid membrane is determined by the aggregation of Penetratin or SUVs, both of which will help it transition from α-state to β-state. Therefore, when the SUV solution is diluted to a lower concentration, the SUV aggregation can be reduced, and the β-state is not easy to form. The experimental results show that the P/L at 1/20 when the SUV solution is diluted from 6.36mM to 318 μM. It can be found that the Penetratin is in the β-state. However, if it is diluted to a lower concentration, the proportion of the β-state gradually decreases. When the concentration is less than 70.7μM, it can be found that the β-state can be transformed entirely into an α-state, which can effectively support the inference of this paper.

Keywords: penetrating peptides, Penetratin, circular dichroism, β-amyloid, SUV solution