Back

Membrane-active Polymers: NCMNP13-x, NCMNP21-x and NCMNP21b-x for Membrane Protein Structural Biology

Trinh, T. K. H.; Catalano, C.; Guo, Y.

2022-01-11 biochemistry
10.1101/2022.01.10.475744 bioRxiv
Show abstract

Membrane proteins are a ubiquitous group of bio-macromolecules responsible for many crucial biological processes and serve as drug targets for a wide range of modern drugs. Detergent-free technologies such as styrene-maleic acid lipid particles (SMALP), diisobutylene-maleic acid lipid particles (DIBMALP), and native cell membrane nanoparticles (NCMN) systems have recently emerged as revolutionary alternatives to the traditional detergent-based approaches for membrane protein research. NCMN systems aim to create a membrane-active polymer library suitable for high-resolution structure determination. Herein, we report our design, synthesis, characterization and comparative application analyses of three novel classes of NCMN polymers, NCMNP13-x, NCMNP21-x and NCMNP21b-x. Although each NCMN polymer can solubilize various model membrane proteins and conserve native lipids into NCMN particles, only the NCMNP21b-x series reveals lipid-protein particles with good buffer compatibility and high homogeneity suitable for single-particle cryo-EM analysis. Consequently, the NCMNP21b-x polymers that bring out high-quality NCMN particles are particularly attractive for membrane protein structural biology. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/475744v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@dbc1f3org.highwire.dtl.DTLVardef@19a5ff0org.highwire.dtl.DTLVardef@10beceorg.highwire.dtl.DTLVardef@15ec66a_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDemonstrate straightforward strategies for tailoring styrene-maleic co-polymer (SMA) that revealed novel buffer compatible polymers, NCMNP13-50, NCMNP21-20 and NCMNP21b-x. C_LIO_LIElucidate how modification factors alter the membrane-active properties of these polymers, i.e., membrane protein extraction efficiency, morphology, etc. C_LIO_LIProvide valuable insights into the rational design of membrane-active polymers for membrane protein structural biology. C_LIO_LINCMNP21b-x polymers are highly compatible with high-resolution structure determination using an emerging technique, cryo-EM. C_LI

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.