2016
DOI: 10.1042/bst20160049
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Overcoming bottlenecks in the membrane protein structural biology pipeline

Abstract: Correspondence to: Alice Rothnie (+44 121 204 4013 a.rothnie@aston.ac.uk) or Anass Jawhari (+33 649 555 606 ajawhari@calixar.com) Key words:Membrane proteins Structural biology SMALP Calixarenes MNG Solubilisation Abbreviations:EM-Electron Microscopy GPCR-G protein-coupled receptors GNG-Glucose Neopentyl Glycol MSP -Membrane Scaffold Protein MNG-Maltose Neopentyl Glycol NMR-Nuclear magnetic resonance SMA-Styrene Maleic Acid SMALPs -SMA Lipid Particles AbstractMembrane proteins account for a third of the eukary… Show more

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Cited by 47 publications
(32 citation statements)
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“…It was proposed and partially proved that these amphiphiles freeze the monomeric structure of the protein, preventing its aggregation and denaturation, through hydrophobic interactions with the protein membrane region and through a network of salt bridges with the basic residues at the cytosol-membrane interface. With the aim of overcoming what has been indicated as a bottleneck in the membrane protein structural biology, [75] in the latest years other studies appeared where the stabilisation, isolation and characterisation of membrane proteins such as Human Multidrug Resistance Protein 4 [76] and G protein-coupled receptors, [77] using similar calixarene detergents, were reported. A glycocalixarene having glucose units at the upper and an heptyl chain at the lower rim also showed to preserve and stabilise, even over long periods of time, the function of three native membrane proteins.…”
Section: Calixarene-based Detergents For Membrane Proteinsmentioning
confidence: 99%
“…It was proposed and partially proved that these amphiphiles freeze the monomeric structure of the protein, preventing its aggregation and denaturation, through hydrophobic interactions with the protein membrane region and through a network of salt bridges with the basic residues at the cytosol-membrane interface. With the aim of overcoming what has been indicated as a bottleneck in the membrane protein structural biology, [75] in the latest years other studies appeared where the stabilisation, isolation and characterisation of membrane proteins such as Human Multidrug Resistance Protein 4 [76] and G protein-coupled receptors, [77] using similar calixarene detergents, were reported. A glycocalixarene having glucose units at the upper and an heptyl chain at the lower rim also showed to preserve and stabilise, even over long periods of time, the function of three native membrane proteins.…”
Section: Calixarene-based Detergents For Membrane Proteinsmentioning
confidence: 99%
“…However, careful characterisation is required to ensure that the membrane protein retains the correct structure and function, and that it has not been unintentionally compromised by the addition of the solubilising tag. The ability to produce human IMPs in this way opens up the approach for drug discovery applications, where the challenges of producing adequate quantities of purified membrane protein is a major hurdle [31] .…”
Section: Producing Water Soluble Imps With Solubilising Fusion Tagsmentioning
confidence: 99%
“…As cellular gate-keepers, membrane proteins (MPs) account for a third of the eukaryotic proteome and are responsible for a variety of physiological functions [1][2][3][4]. For instance, cells use MPs to transmitt signals into cells, transport ions and molecules, bind to cell surface or a substrate, and catalyze reactions under different conditions [5][6][7][8].…”
Section: Introductionmentioning
confidence: 99%