High-pressure crystallography shows noble gas intervention into protein-lipid interaction and suggests a model for anaesthetic action

• Published in: Communications biology Vol. 5; no. 1; p. 360
• Main Authors: Melnikov, Igor, Orekhov, Philipp, Rulev, Maksim, Kovalev, Kirill, Astashkin, Roman, Bratanov, Dmitriy, Ryzhykau, Yury, Balandin, Taras, Bukhdruker, Sergei, Okhrimenko, Ivan, Borshchevskiy, Valentin, Bourenkov, Gleb, Mueller-Dieckmann, Christoph, van der Linden, Peter, Carpentier, Philippe, Leonard, Gordon, Gordeliy, Valentin, Popov, Alexander
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.04.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45/535/1266; 631/57/2271; 82; 82/80; Anesthesia; Anesthetics; Argon; Argon - chemistry; Argon - pharmacology; Binding sites; Biochemistry, Molecular Biology; Biology; Biomedical and Life Sciences; Condensed Matter; Crystallography; Crystallography, X-Ray; Crystals; Gases; Hydrophobicity; Inert gases; Krypton - chemistry; Krypton - metabolism; Life Sciences; Lipids; Membrane proteins; Physics; Proteins; Structural Biology; Structure-function relationships; X-ray crystallography
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03233-y

In this work we examine how small hydrophobic molecules such as inert gases interact with membrane proteins (MPs) at a molecular level. High pressure atmospheres of argon and krypton were used to produce noble gas derivatives of crystals of three well studied MPs (two different proton pumps and a sodium light-driven ion pump). The structures obtained using X-ray crystallography showed that the vast majority of argon and krypton binding sites were located on the outer hydrophobic surface of the MPs – a surface usually accommodating hydrophobic chains of annular lipids (which are known structural and functional determinants for MPs). In conformity with these results, supplementary in silico molecular dynamics (MD) analysis predicted even greater numbers of argon and krypton binding positions on MP surface within the bilayer. These results indicate a potential importance of such interactions, particularly as related to the phenomenon of noble gas-induced anaesthesia. Noble gases are known to interact with proteins and can be good anaesthetics in hyperbaric conditions. This study identifies argon and krypton binding sites on membrane proteins and proposes as a hypothesis that noble gases, by altering protein/lipid contacts, may affect protein function.