Latest developments in experimental and computational approaches to characterize protein–lipid interactions

Abstract

Understanding the functional roles of all the molecules in cells is an ultimate goal of modern biology. An important facet is to understand the functional contributions from intermolecular interactions, both within a class of molecules (e.g. protein–protein) or between classes (e.g. protein-DNA). While the technologies for analyzing protein–protein and protein–DNA interactions are well established, the field of protein–lipid interactions is still relatively nascent. Here, we review the current status of the experimental and computational approaches for detecting and analyzing protein–lipid interactions. Experimental technologies fall into two principal categories, namely solution-based and array-based methods. Computational methods include large–scale data-driven analyses and predictions/dynamic simulations based on prior knowledge of experimentally identified interactions. Advances in the experimental technologies have led to improved computational analyses and vice versa, thereby furthering our understanding of protein–lipid interactions and their importance in biological systems.

Lipidomics in Health and Diseases - Beyond the Analysis of Lipids

“…Lipids with a phosphate functional group are classified as phospholipids, which account for ~60% lipid mass in eukaryotic cells [19]. Phospholipids, including glycerophospholipids and phosphosphingolipids, are the primary building blocks of biological membranes and the precursors for signaling molecules such as inositol triphosphate and diacylglycerol, which are produced by various phospholipases [20].…”

Detecting Protein–Glycolipid Interactions Using Glycomicelles and CaR-ESI-MS

“…An alternative approach is to incorporate the GLs in a lipid monolayer or bilayer, such that the protein-GL interactions can be studied in a more native-like environment [10]. For such studies, a variety of different model membranes have been used to solubilize the GLs, including supported lipid bilayers, liposomes, micelles, bicelles, nanodiscs, and picodiscs [11][12][13][14], and the protein-GL interactions probed using diverse analytical techniques (e.g., fluorescence, nuclear magnetic resonance (NMR), and SPR spectroscopy) [15][16][17][18].between water-soluble lectins and GLs, solubilized using nanodiscs (NDs), have been detected using the catch-andrelease (CaR)-ESI-MS assay [19,20]. Nanodiscs are discoidal phospholipid bilayers surrounded by two copies of an amphipathic membrane scaffold protein [12,13].…”

Sensitivity of peripheral membrane proteins to the membrane context: A case study of phosphatidylserine and the TIM proteins

“…The Enzyme-Linked Immunosorbent Assays (ELISA), Surface Plasmon Resonance (SPR), Langmuir monolayer systems, lipid microarrays, liposome microarrays, fluorescence spectroscopy, and Isothermal Titration Calorimetry (ITC) have been integral in measuring the binding affinity of peripheral membrane-binding proteins for lipids [29–32]. Fluorescence spectroscopy and ITC have the advantage of measuring the binding of liposomes, soluble unilamellar lipid vesicles that require no membrane immobilization and serve as models for natural membrane structures of various sizes such as vesicles, organelle membranes, or cell membranes [33].…”