Cation-π Interactions and their Functional Roles in Membrane Proteins

Daniel T Infield; Ali Rasouli; Grace D Galles; Christophe Chipot; Emad Tajkhorshid; Christopher A Ahern

doi:10.1016/j.jmb.2021.167035

Cation-π Interactions and their Functional Roles in Membrane Proteins

J Mol Biol. 2021 Aug 20;433(17):167035. doi: 10.1016/j.jmb.2021.167035. Epub 2021 May 4.

Authors

Daniel T Infield¹, Ali Rasouli², Grace D Galles³, Christophe Chipot⁴, Emad Tajkhorshid², Christopher A Ahern¹

Affiliations

¹ Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52246, USA.
² Theoretical and Computational Biophysics Group, NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Biochemistry, and Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
³ Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52246, USA; Unnatural Protein Facility, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
⁴ Theoretical and Computational Biophysics Group, NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Laboratoire International Associé CNRS-University of Illinois, Unité mixte de recherche n°70a9, Université de Lorraine, France; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Abstract

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.

Keywords: GPCR; cation-π interactions; computational chemistry; genetic code expansion; ion channels.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Cations / metabolism*
Humans
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Membrane Proteins / metabolism*
Thermodynamics

Substances

Cations
Membrane Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding