![]() ![]() Hence, the available information on the lipid content of xMALPs derived from biological membranes is very limited, and it is unclear whether the different xMAs show preferential solubilization of certain protein species or lipid classes. Only a few studies have analyzed the lipid content of SMALPs, focusing on phospholipids (PLs). This finding made us question to what extent xMA nanodiscs resemble the native membrane and what lipids are present in the xMALPs. However, we observed that the activity differed depending on the chemical properties of the xMA used. In addition, rhomboid activity resembled more that in the membrane when in xMALPs than when in micelles. In our previous work, we found xMALPs to stabilize fragile rhomboid proteases that self-process when in detergent micelles 7. For example, they enabled the structure determination of the alternative complex III by cryogenic electron microscopy 5 and the elucidation of naturally occurring oligomeric states of various MPs 6. ![]() Since their introduction, xMALPs have resulted in various exciting findings. Another example is SMA-SH 4, the structure of which contains thiol groups that can act as chemical handles for reaction with fluorophores or other functional moieties. For example, diisobutylene maleic acid (DIBMA) has aliphatic alkyl chains instead of aromatic groups, avoiding ultraviolet (UV) absorption and allowing the use of optical spectroscopic techniques such as circular dichroism. These new xMAs have improved chemical properties or incorporate chemical modifications that broaden the downstream applications of xMA lipid protein nanodiscs (xMALPs). In addition to SMA, several other maleic acid copolymers (xMAs) have been synthesized as nanodisc-forming agents (Fig. Hence, SMAs can fully by-pass the use of detergents. SMAs can extract MPs with their lipid microenvironment, forming styrene maleic acid lipid particles (SMALPs) soluble in aqueous buffer. This de-lipidation can compromise structural integrity and may cause problems with protein activity or stability.Ī decade ago, styrene maleic acid (SMA) copolymers were reported as nanodisc-forming agents. Traditionally, this has been achieved with detergents, which isolate MPs in micelles by destroying the lipid bilayer. Purification of MPs requires a prior solubilization step. Unfortunately, MPs are less well understood than their soluble counterparts because of their more difficult expression and purification procedures 3. Overall, MPs form two-thirds of the total druggable targets in the cell 1, 2. For example, the membrane-bound kinase epidermal growth factor receptor plays a role in different types of cancer and the malfunctioning of the ion channel N-Methyl- d-Aspartate receptor contributes to Alzheimer’s disease pathophysiology. Certain specific MPs have been linked to various human diseases. Membrane proteins (MPs) are essential players in a wide variety of essential physiological processes. ![]()
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