Membrane biology visualized in nanometer-sized discs formed by styrene maleic acid polymers

Abstract

Discovering how membrane proteins recognize signals and passage molecules remains challenging. Life depends on compartmentalizing these processes into dynamic lipid bilayers that are technically difficult to work with. Several polymers have proven adept at separating the responsible machines intact for detailed analysis of their structures and interactions. Styrene maleic acid (SMA) co-polymers efficiently solubilize membranes into native nanodiscs and, unlike amphipols and membrane scaffold proteins, require no potentially destabilizing detergents. Here we review progress with the SMA lipid particle (SMALP) system and its impacts including three dimensional structures and biochemical functions of peripheral and transmembrane proteins. Polymers systems are emerging to tackle the remaining challenges for wider use and future applications including in membrane proteomics, structural biology of transient or unstable states, and discovery of ligand and drug-like molecules specific for native lipid-bound states.

Membrane Solubilization by Styrene-Maleic Acid Copolymers: Delineating the Role of Polymer Length

“…Styrene-maleic acid (SMA) copolymers are in the spotlight of membrane protein research because of their ability to solubilize lipid membranes into nanodisks (for reviews, see (1,2)). SMA-mediated solubilization offers many advantages over conventional solubilization methods based on the use of detergents, including retention of the membrane architecture (i.e., lipid bilayer conformation) in nanodisks (3,4) and the suitability of nanodisk particles for analysis by biophysical techniques such as NMR (5,6), turbidimetry (7,8), and calorimetry (3,9,10).…”

Conserved His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity

“…While a reconstitution approach provides for a controlled and defined lipid environment, the necessity of an initial detergent-based extraction step may disrupt protein-lipid interactions integral to the structural integrity of transmembrane segments. In contrast with nanodisc reconstitution, SMA copolymers extract membrane proteins directly from the lipid bilayer, eschewing detergent entirely and permitting the study of membrane proteins in the presence of endogenous lipids (51, 52) and, in principle, maintaining the protein-lipid interactions that occur at the cell membrane (53).…”

Beyond detergent micelles: The advantages and applications of non-micellar and lipid-based membrane mimetics for solution-state NMR

“…Solution-state NMR experiments involving SMALPs have been limited to membrane attached proteins [102] with no integral MPs reported so far. The reason for this might be the larger size inhomogeneity of SMALPs compared to protein based nanodisc systems [103]. Such variations would not affect the spectral quality of membrane attached proteins, since the soluble domains do not interact directly with the nanodisc.…”