Work

The Evolution of Lipids from Solvents to Substrates

Year: 2025

Type: review

Abstract: While the role of water in soluble protein structure and function is well-established, the analogous role of lipids as a solvent for membrane proteins is less understood. Bacterial membranes exhibit extraordinary lipid diversity, with Escherichia coli synthesizing over 1,800 distinct glycerophospholipids. This lipid diversity gives rise to bulk membrane properties and specific lipid–lipid and lipid–protein interactions that directly affect α-IMP folding, assembly, and function. In this review, we use the same thermodynamic framework for understanding the solvation of soluble proteins to examine bacterial α-helical integral membrane protein (α-IMP) interactions with chemically diverse lipid environments. We propose that preferential solvent interactions were essential evolutionary drivers that enabled lipids to evolve as protein cofactors and substrates, with lipid chemical diversity creating unique evolutionary pressures distinct from those of aqueous systems.

Source: Annual Review of Biophysics

DOI: 10.1146/annurev-biophys-021424-012603

Authors: Aninda Dutta, Charlotte Hannis, Nathan Feinberg, Linda Columbus

Institution: University of Virginia

Language: English

Topic: Lipid Membrane Structure and Behavior

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funder: National Institute of General Medical Sciences

Award: Biophysical understanding of pathogen-host membrane protein interactions for drug discovery and delivery