Cation-π Interactions and their Functional Roles in Membrane Proteins

• Published in: Journal of molecular biology Vol. 433; no. 17; p. 167035
• Main Authors: Infield, Daniel T., Rasouli, Ali, Galles, Grace D., Chipot, Christophe, Tajkhorshid, Emad, Ahern, Christopher A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 20.08.2021; Elsevier
• Subjects: Biological Physics; cation-π interactions; Cations - metabolism; Chemical Sciences; computational chemistry; genetic code expansion; GPCR; Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; ion channels; Membrane Proteins - metabolism; Physics; Thermodynamics; cation-π interactions; GPCR; genetic code expansion; computational chemistry; ion channels
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2021.167035

[Display omitted] •Physicochemical characteristics are summarized.•Cation- π abundance is in membrane proteins assessed via automated structural analysis.•Methods to assess cation- π interactions are discussed.•Examples of cation- π interactions in diverse protein types are highlighted. Cation-π interactions arise as a result of strong attractive forces between positively charged entities and the π-electron cloud of aromatic groups. The physicochemical characteristics of cation-π interactions are particularly well-suited to the dual hydrophobic/hydrophilic environment of membrane proteins. As high-resolution structural data of membrane proteins bring molecular features into increasingly sharper view, cation-π interactions are gaining traction as essential contributors to membrane protein chemistry, function, and pharmacology. Here we review the physicochemical properties of cation-π interactions and present several prominent examples which demonstrate significant roles for this specialized biological chemistry.