Product Spotlight: Using PMA-Lipid Nanoparticles to Solubilize GPCRs without Detergents

Posted on September 02, 2021

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Detergent-less solubilization of proteins is the new trend in protein research, and Avanti has you covered with a unique polymer solution. Avanti exclusively offers polymethacrylate (PMA) copolymer for the production of PMA-lipid nanoparticle (NP) nanodiscs. PMA offers many advantages to the commonly used SMA polymer.

There are many limitations to using detergents for GPCR solubilization such as typically low thermostability and lower purification yields. As previously mentioned, a common way to solubilize proteins without the use of detergents involves using SMA-NP nanodiscs. These nanodiscs result in the protein being solubilized in a native-like bilayer environment with retention of receptor functionality. Several factors complicate the usage of SMA in membrane protein solubilization:

  • Divalent cations at low mM concentrations cause the precipitation of SMA
  • Commonly used buffer cations such as Mg and Ca are unusable
  • SMA may interact with resins used during the purification process (Ni chelating resins and gel filtration resins in particular)
  • The styrene groups of SMA absorb UV which can interfere with quantification methods that rely on UV detection

This is where PMA offers a viable alternative as a detergent-free solubilization method. They have been shown to solubilize lipid-bilayers into nanodiscs and are formed from butylmethacrylate and cationic methacroylcholine chloride monomers. Forming a copolymer from these monomers results in a maleic acid and styrene-free copolymer.

Research at Oxford University has recently shown that PMA-NP nanodiscs are capable of the solubilization and subsequent purification of the GPCR, NTSR1. The PMA solubilized NTSR1 GPCR resulted in greater stimulation, indicating that PMA solubilizes NTSR1 into a more native conformation than the detergent solubilization alternative. Furthermore, PMA proved to be compatible with commonly used purification techniques and mM concentrations of divalent cations. This alternative provides wide utility in membrane protein solubilization and purification especially in cases where SMA is less effective or not viable.

If your membrane protein research is stalled due to ineffective solubilization using a polymer-NP nanodisc, check out Avanti’s PMA copolymer and get your research back on track today!

Check out our PMA, and click HERE to read the full article on the solubilization of NTRS1 with PMA nanodiscs.