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Fluoride permeation mechanism of the Fluc channel in liposomes revealed by solid-state NMR

Solid-state nuclear magnetic resonance (ssNMR) methods can probe the motions of membrane proteins in liposomes at the atomic level and propel the understanding of biomolecular processes for which static structures cannot provide a satisfactory description. In this work, we report our study on the fl...

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Detalles Bibliográficos
Autores principales: Zhang, Jin, Song, Dan, Schackert, Florian Karl, Li, Juan, Xiang, Shengqi, Tian, Changlin, Gong, Weimin, Carloni, Paolo, Alfonso-Prieto, Mercedes, Shi, Chaowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10446490/
https://www.ncbi.nlm.nih.gov/pubmed/37611110
http://dx.doi.org/10.1126/sciadv.adg9709
Descripción
Sumario:Solid-state nuclear magnetic resonance (ssNMR) methods can probe the motions of membrane proteins in liposomes at the atomic level and propel the understanding of biomolecular processes for which static structures cannot provide a satisfactory description. In this work, we report our study on the fluoride channel Fluc-Ec1 in phospholipid bilayers based on ssNMR and molecular dynamics simulations. Previously unidentified fluoride binding sites in the aqueous vestibules were experimentally verified by (19)F-detected ssNMR. One of the two fluoride binding sites in the polar track was identified as a water molecule by (1)H-detected ssNMR. Meanwhile, a dynamic hotspot at loop 1 was observed by comparing the spectra of wild-type Fluc-Ec1 in variant buffer conditions or with its mutants. Therefore, we propose that fluoride conduction in the Fluc channel occurs via a “water-mediated knock-on” permeation mechanism and that loop 1 is a key molecular determinant for channel gating.