GxxxG Motif Stabilize Ion-Channel like Pores through C α -H···O Interaction in Aβ (1-40).
Carola RandoGiuseppe GrassoDibakar SarkarMichele Francesco Maria SciaccaLorena Maria CucciAlessia CosentinoGiuseppe ForteMartina PannuzzoCristina SatrianoAnirban BhuniaCarmelo La RosaPublished in: International journal of molecular sciences (2023)
Aβ (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 Cα-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.
Keyphrases
- molecular dynamics
- molecular dynamics simulations
- amino acid
- electronic health record
- density functional theory
- dna binding
- big data
- systematic review
- high resolution
- oxidative stress
- dna damage
- ionic liquid
- dna damage response
- transcription factor
- mass spectrometry
- small molecule
- quantum dots
- crystal structure
- transition metal