scholarly journals Synthesis and Evaluation of a Library of Alternating Amphipathic Copolymers to Solubilize and Study Membrane Proteins

2021 ◽  
Author(s):  
Adrian H. Kopf ◽  
Odette Lijding ◽  
Barend O. W. Elenbaas ◽  
Martijn C. Koorengevel ◽  
Justyna M. Dobruchowska ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Maleic Acid ◽  
Rational Design ◽  
Extraction Efficiency ◽  
Yeast Mitochondria ◽  
Electronic Effects ◽  
Alternating Copolymers ◽  
Polymer Properties

Amphipathic copolymers such as poly(styrene-maleic acid) (SMA) are promising tools for the facile extraction of membrane proteins (MPs) into native nanodiscs. Here, we designed and synthesized a library of well-defined alternating copolymers of SMA analogues in order to elucidate polymer properties that are important for MP solubilization and stability. MP extraction efficiency was determined using KcsA from E.coli membranes and general solubilization efficiency was investigated via turbidimetry experiments on membranes of E.coli, yeast mitochondria and synthetic lipids. Remarkably, halogenation of SMA copolymers dramatically improved solubilization efficiency in all systems, while substituents on the copolymer backbone improved resistance to Ca2+. Relevant polymer properties were found to include hydrophobic balance, size and positioning of substituents, rigidity and electronic effects. The library thus contributes to the rational design of copolymers for the study of MPs.

Protein Extraction Efficiency and Selectivity of Esterified Styrene–Maleic Acid Copolymers in Thylakoid Membranes

2021 ◽  
Author(s):  
Nathan G. Brady ◽  
Cameron E. Workman ◽  
Bridgie Cawthon ◽  
Barry D. Bruce ◽  
Brian K. Long
Keyword(s):  
Maleic Acid ◽  
Extraction Efficiency ◽  
Protein Extraction ◽  
Thylakoid Membranes

The binding of cationic surfactants by hydrophobic alternating copolymers of maleic acid

1986 ◽  
Vol 20 (4) ◽  
pp. 289-301 ◽  
Author(s):  
Toshio Shimizu ◽  
Mitsutaka Seki ◽  
Jan C.T. Kwak
Keyword(s):  
Maleic Acid ◽  
Cationic Surfactants ◽  
Alternating Copolymers

Evaluation of commercially available styrene-co-maleic acid polymers for the extraction of membrane proteins from spinach chloroplast thylakoids

2019 ◽  
Vol 114 ◽  
pp. 485-500 ◽  
Author(s):  
Olena Korotych ◽  
Jyotirmoy Mondal ◽  
Kerim M. Gattás-Asfura ◽  
Jessica Hendricks ◽  
Barry D. Bruce
Keyword(s):  
Membrane Proteins ◽  
Maleic Acid ◽  
Spinach Chloroplast

Cryo-Electron Microscopy: Moving Beyond X-Ray Crystal Structures for Drug Receptors and Drug Development

2020 ◽  
Vol 60 (1) ◽  
pp. 51-71 ◽  
Author(s):  
Javier García-Nafría ◽  
Christopher G. Tate
Keyword(s):  
Membrane Proteins ◽  
G Protein ◽  
Rational Design ◽  
Protein Complexes ◽  
Host Cells ◽  
X Ray ◽  
X Ray Crystallography ◽  
Receptor Modulation ◽  
Lipid Environment ◽  
Drug Receptors

Electron cryo-microscopy (cryo-EM) has revolutionized structure determination of membrane proteins and holds great potential for structure-based drug discovery. Here we discuss the potential of cryo-EM in the rational design of therapeutics for membrane proteins compared to X-ray crystallography. We also detail recent progress in the field of drug receptors, focusing on cryo-EM of two protein families with established therapeutic value, the γ-aminobutyric acid A receptors (GABAARs) and G protein–coupled receptors (GPCRs). GABAARs are pentameric ion channels, and cryo-EM structures of physiological heteromeric receptors in a lipid environment have uncovered the molecular basis of receptor modulation by drugs such as diazepam. The structures of ten GPCR–G protein complexes from three different classes of GPCRs have now been determined by cryo-EM. These structures give detailed insights into molecular interactions with drugs, GPCR–G protein selectivity, how accessory membrane proteins alter receptor–ligand pharmacology, and the mechanism by which HIV uses GPCRs to enter host cells.

scholarly journals Disentangling the size-dependent geometric and electronic effects of palladium nanocatalysts beyond selectivity

2019 ◽  
Vol 5 (1) ◽  
pp. eaat6413 ◽  
Author(s):  
Hengwei Wang ◽  
Xiang-Kui Gu ◽  
Xusheng Zheng ◽  
Haibin Pan ◽  
Junfa Zhu ◽  
...  
Keyword(s):  
Metal Nanoparticles ◽  
Rational Design ◽  
Aerobic Oxidation ◽  
Atomic Layer ◽  
Electronic Effects ◽  
Coordination Sites ◽  
Layer Deposition ◽  
Palladium Nanocatalysts ◽  
The Right ◽  
Site Selective

The prominent size effect of metal nanoparticles shapes decisively nanocatalysis, but entanglement of the corresponding geometric and electronic effects prevents exploiting their distinct functionalities. In this work, we demonstrate that in palladium (Pd)–catalyzed aerobic oxidation of benzyl alcohol, the geometric and electronic effects interplay and compete so intensively that both activity and selectivity showed in volcano trends on the Pd particle size unprecedentedly. By developing a strategy of site-selective blocking via atomic layer deposition along with first principles calculations, we disentangle these two effects and unveil that the geometric effect dominates the right side of the volcano with larger-size Pd particles, whereas the electronic effect directs the left of the volcano with smaller-size Pd particles substantially. Selective blocking of the low-coordination sites prevents formation of the undesired by-product beyond the volcano relationship, achieving a remarkable benzaldehyde selectivity and activity at the same time for 4-nm Pd. Disentangling the geometric and electronic effects of metal nanoparticles opens a new dimension for rational design of catalysts.

Amphiphilic Acenaphthylene−Maleic Acid Light-Harvesting Alternating Copolymers:  Reversible Addition−Fragmentation Chain Transfer Synthesis and Fluorescence

2005 ◽  
Vol 38 (8) ◽  
pp. 3475-3481 ◽  
Author(s):  
Ming Chen ◽  
Kenneth P. Ghiggino ◽  
Albert W. H. Mau ◽  
Wolfgang H. F. Sasse ◽  
San H. Thang ◽  
...  
Keyword(s):  
Maleic Acid ◽  
Chain Transfer ◽  
Light Harvesting ◽  
Alternating Copolymers ◽  
Reversible Addition

Membrane proteins: is the future disc shaped?

2016 ◽  
Vol 44 (4) ◽  
pp. 1011-1018 ◽  
Author(s):  
Sarah C. Lee ◽  
Naomi L. Pollock
Keyword(s):  
Membrane Proteins ◽  
Maleic Acid ◽  
Membrane Lipids ◽  
Biological Membranes ◽  
Structure And Function ◽  
Amphiphilic Copolymer ◽  
New Approach ◽  
Analysis Techniques ◽  
Lipid Particles ◽  
And Function

The use of styrene maleic acid lipid particles (SMALPs) for the purification of membrane proteins (MPs) is a rapidly developing technology. The amphiphilic copolymer of styrene and maleic acid (SMA) disrupts biological membranes and can extract membrane proteins in nanodiscs of approximately 10 nm diameter. These discs contain SMA, protein and membrane lipids. There is evidence that MPs in SMALPs retain their native structures and functions, in some cases with enhanced thermal stability. In addition, the method is compatible with biological buffers and a wide variety of biophysical and structural analysis techniques. The use of SMALPs to solubilize and stabilize MPs offers a new approach in our attempts to understand, and influence, the structure and function of MPs and biological membranes. In this review, we critically assess progress with this method, address some of the associated technical challenges, and discuss opportunities for exploiting SMA and SMALPs to expand our understanding of MP biology.

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