Insights into the Role of Membrane Lipids in the Structure, Function and Regulation of Integral Membrane Proteins

Abstract

Membrane proteins exist within the highly hydrophobic membranes surrounding cells and organelles, playing key roles in cellular function. It is becoming increasingly clear that the membrane does not just act as an appropriate environment for these proteins, but that the lipids that make up these membranes are essential for membrane protein structure and function. Recent technological advances in cryogenic electron microscopy and in advanced mass spectrometry methods, as well as the development of alternative membrane mimetic systems, have allowed experimental study of membrane protein–lipid complexes. These have been complemented by computational approaches, exploiting the ability of Molecular Dynamics simulations to allow exploration of membrane protein conformational changes in membranes with a defined lipid content. These studies have revealed the importance of lipids in stabilising the oligomeric forms of membrane proteins, mediating protein–protein interactions, maintaining a specific conformational state of a membrane protein and activity. Here we review some of the key recent advances in the field of membrane protein–lipid studies, with major emphasis on respiratory complexes, transporters, channels and G-protein coupled receptors.

Endothelial Cell Plasma Membrane Biomechanics Mediates Effects of Pro-Inflammatory Factors on Endothelial Mechanosensors: Vicious Circle Formation in Atherogenic Inflammation

“…The "force-from-lipid" model suggests the gating of mechanosensitive ion channels with inputs from the lipid bilayer, while the "force-from-filament" model suggests primary roles of the extracellular matrix and intracellular cytoskeleton (CSK) in the mechanical activation of ion channels [32]. Great efforts have been devoted to deciphering the multi-ple effects exerted by membrane lipids on the structure and function of transmembrane proteins [33][34][35][36][37][38][39][40][41][42][43][44].…”

“…Membranes 2022, 12, x FOR PEER REVIEW 3 of 20 with inputs from the lipid bilayer, while the "force-from-filament" model suggests primary roles of the extracellular matrix and intracellular cytoskeleton (CSK) in the mechanical activation of ion channels [32]. Great efforts have been devoted to deciphering the multiple effects exerted by membrane lipids on the structure and function of transmembrane proteins [33][34][35][36][37][38][39][40][41][42][43][44]. Two major types of physical effects, integral membrane proteins or ion channels, are expected to draw from the hosting lipid bilayer due to its profiles of electrical charges and mechanical properties [43].…”

Stromal Fibroblasts Counteract the Caveolin-1-Dependent Radiation Response of LNCaP Prostate Carcinoma Cells

“…Cholesterol is thereby displaced-at least partially-by ceramide and thus, the association of cholesterol with CAV1 is decreased. Lipid membranes were shown to generate two distinct types of condensed GM1 gangliosides (sialic acid-containing oligosaccharides covalently attached to ceramide lipids)-containing microdomains: rapidly formed but short-lived GM1 clusters that are formed in ceramide-rich domains and are predominantly involved in apoptosis, and long-lasting high-density GM1 condensations in the liquidordered phase, namely raft-like regions accounting for proliferation-promoting signaling (50,51). As a more permanent plasma membrane modification, the latter one might account for signalosome-amplified signaling events upon CAV1 being present within the plasma membrane.…”

Four Cholesterol-Recognition Motifs in the Pore-Forming and Translocation Domains of Adenylate Cyclase Toxin Are Essential for Invasion of Eukaryotic Cells and Lysis of Erythrocytes

“…This transition from a water-soluble structure to a distinct membrane-associated protomer involves structural rearrangements of the protein in the membrane environment. Membrane lipids are important regulators that can influence the process of proteins insertion in two ways, indirectly, by modulating the biophysical properties of the lipid bilayer such as fluidity, phase segregation, bilayer thickness, tension, etc., which may affect protein structure and function [ 5 , 6 , 7 ], or directly, through specific lipid-protein interactions [ 8 , 9 , 10 ].…”