Abstract
The omics disciplines remain largely distinct sciences due to the necessity of separating molecular classes for different assays. For example, water-soluble and lipid bilayer-bound proteins and metabolites are usually studied separately. Nonetheless, it is at the interface between these sciences where biology happens. That is, lipid-interacting proteins typically recognize and transduce signals and regulate the flow of metabolites in the cell. Technologies are emerging to converge the omics. It is now possible to separate intact membrane:protein assemblies (memteins) directly from intact cells or cell membranes. Such complexes mediate complete metabolon, receptor, channel, and transporter functions. The use of poly(styrene-co-maleic acid) (SMA) copolymers has allowed their separation in a single step without any exposure to synthetic detergents or artificial lipids. This is a critical development as these agents typically strip away biological lipids, signals, and metabolites from their physiologically-relevant positions on proteins. The resulting SMA lipid particles (SMALPs) represent native nanodiscs that are suitable for elucidation of structures and interactions that occur in vivo. Compatible tools for resolving the contained memteins include X-ray diffraction (XRD), cryo-electron microscopy (cryoEM), mass spectrometry (MS), and nuclear magnetic resonance (NMR) spectroscopy. Recent progress shows that memteins are more representative than naked membrane proteins devoid of natural lipid and is driving the development of next generation polymers.
Highlights
Featured Application: Nanodiscs formed by styrene maleic acid copolymers allow separation of biologically intact protein complexes with native ligands for syst-OMICS analysis
The design of SMA as an effective mild solubilizer of virtually any lipid bilayer or memtein relies on the short styrene sidechains which insert into hydrophobic material [20]
These studies and many others document the attractive option that SMA polymers present for solubilizing a wide diversity of memteins, including those monomers and multimers that are unstable, low abundance, or lipid-dependent
Summary
Proteomics involves analysis of all the proteins from an organelle or cellular system. The resulting peptides are fractionated and identified based on MS-based fragmentation patterns This approach reduces the complexity of the original heterogeneous mixtures and bypasses the problems associated with analyzing intact proteins through ionization and MS characterization. The detergents, such as sodium dodecyl sulfate (SDS), that are commonly used to solubilize or unfold the proteins to enhance protease access are problematic. A special class of synthetic polymers have been invented for detergent-free separation of native membrane:protein complexes from biological matter into nanodiscs along with their associated ligands and lipids for analysis by virtually any structural or biophysical assay
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