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

Autor: Rando, Carola, Grasso, Giuseppe, Sarkar, Dibakar, Sciacca, Michele Francesco Maria, Cucci, Lorena Maria, Cosentino, Alessia, Forte, Giuseppe, Pannuzzo, Martina, Satriano, Cristina, Bhunia, Anirban, Rosa, Carmelo La
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences
Volume 24
Issue 3
Pages: 2192
ISSN: 1422-0067
DOI: 10.3390/ijms24032192
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje