GxxxG Motif Stabilize Ion-Channel like Pores through Cα-H...O Interaction in Aβ (1-40)

A beta (1-40) can transfer from the aqueous phase to the bilayer and thus form stable ion-channel-like pores where the protein has alpha-helical conformation. The stability of the pores is due to the presence of the GXXXG motif. It has been reported that these ion-channel-like pores are stabilized by a C alpha-H...O hydrogen bond that is established between a glycine of the GXXXG sequence of an alpha-helix and another amino acid of a vicinal alpha-helix. However, conflicting data are reported in the literature. Some authors have suggested that hydrogen bonding does not have a stabilizing function. Here we synthesized pentapeptides having a GXXXG motif to explore its role in pore stability. We used molecular dynamics simulations, quantum mechanics, and experimental biophysical techniques to determine whether hydrogen bonding was formed and had a stabilizing function in ion-channel-like structures. Starting from our previous molecular dynamics data, molecular quantum mechanics simulations, and ATR data showed that a stable ion-channel-like pore formed and a band centered at 2910 cm(-1) was attributed to the interaction between Gly 7 of an alpha-helix and Asp 23 of a vicinal alpha-helix.

Automated summary

The role of hydrogen bonding in the stability of ion-channel-like pores formed by pentapeptides containing a GXXXG motif was investigated. Molecular dynamics simulations, quantum mechanics, and experimental biophysical techniques revealed that the stability of the pores is maintained by a C alpha-H...O hydrogen bond formed between a glycine in the GXXXG sequence and another amino acid in a neighboring α-helix.