Tandem neopentyl glycol maltosides (TNMs) for membrane protein stabilisation

Bae, Hyoung Eun; Mortensen, Jonas S.; Ribeiro, Orquídea; Du, Yang; Ehsan, Muhammad; Kobilka, Brian K.; Løland, Claus J.; Byrne, Bernadette; Chae, Pil Seok

doi:10.1039/c6cc06147h

Cited by 13 publications

(9 citation statements)

References 41 publications

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“…The use of a specific mammalian cell line HEK293-GnTI -, which produces truncated N-glycosylation or the treatment with the enzymes EndoH or PNGaseF can address this problem (Thomas and Tate 2014). Once large amounts of fully functional receptor have been expressed, then it needs to be purified in a functional state, and the recent development of novel mild detergents has been critical for increased successes of this step (Bae et al 2016;Hussain et al 2016). Crystallisation remains a real challenge, but the revival and further development of the lipidic cubic phase technique has been pivotal in the crystallisation success of GPCRs (Huang et al 2016).…”

Section: Towards the High-resolution Structures Of Chemosensory Receptorsmentioning

confidence: 99%

Structure–Function Relationships of Olfactory and Taste Receptors

et al. 2018

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The field of chemical senses has made major progress in understanding the cellular mechanisms of olfaction and taste in the past 2 decades. However, the molecular understanding of odor and taste recognition is still lagging far behind and will require solving multiple structures of the relevant full-length receptors in complex with native ligands to achieve this goal. However, the development of multiple complimentary strategies for the structure determination of G protein-coupled receptors (GPCRs) makes this goal realistic. The common conundrum of how multi-specific receptors that recognize a large number of different ligands results in a sensory perception in the brain will only be fully understood by a combination of high-resolution receptor structures and functional studies. This review discusses the first steps on this pathway, including biochemical and physiological assays, forward genetics approaches, molecular modeling, and the first steps towards the structural biology of olfactory and taste receptors.

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Section: Towards the High-resolution Structures Of Chemosensory Receptorsmentioning

confidence: 99%

Structure–Function Relationships of Olfactory and Taste Receptors

et al. 2018

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“…Introduced less than a decade ago, it has confidently landed in top 10 of the most used detergents in our analysis. The further design of this class of detergents is still ongoing; very recently the same group presented so-called tandem-neopentyl glycol maltosides [80]. Another example is the development of calixarenes [45]-this novel class of detergents is built on a rigid calixarene scaffold to which hydrophobic tail and hydrophilic and charged headgroups are attached.…”

Section: Discussion and Outlookmentioning

confidence: 99%

An Overview of the Top Ten Detergents Used for Membrane Protein Crystallization

2017

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Abstract:To study integral membrane proteins, one has to extract them from the membrane-the step that is typically achieved by the application of detergents. In this mini-review, we summarize the top 10 detergents used for the structural analysis of membrane proteins based on the published results. The aim of this study is to provide the reader with an overview of the main properties of available detergents (critical micelle concentration (CMC) value, micelle size, etc.) and provide an idea of what detergents to may merit further study. Furthermore, we briefly discuss alternative solubilization and stabilization agents, such as polymers.

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“…However, the current tripod amphiphiles differ from previous versions (TPAs and TMNs). 22,40 The previous tripod amphiphiles have branching points localized in both hydrophilic and hydrophobic portions rather than at the central part of the molecules. As the branching points were connected via a thin alkyl spacer, these previous versions likely contain large empty spaces in their micelle interiors, particularly in the hydrophilic-hydrophobic interface.…”

Section: Detergent Structures and Physical Characterizationsmentioning

confidence: 99%

Conformationally Restricted Monosaccharide-Cored Glycoside Amphiphiles: The Effect of Detergent Headgroup Variation on Membrane Protein Stability

et al. 2019

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Detergents are widely used to isolate membrane proteins from lipid bilayers, but many proteins solubilized in conventional detergents are structurally unstable. Thus, there is major interest in the development of novel amphiphiles to facilitate membrane protein research. In the present study, we have designed and synthesized novel amphiphiles with a rigid scyllo-inositol core, designated scyllo-inositol glycosides (SIGs). Varying the head group structure allowed the preparation of three sets of SIGs that were evaluated for their effects on membrane protein stability. When tested with a few model membrane proteins, representative SIGs conferred enhanced stability to the membrane proteins compared to a gold standard conventional detergent (DDM). Of the novel amphiphiles, a SIG designated STM-12 was most effective at preserving the stability of the multiple membrane proteins tested here. In addition, a comparative study of the three sets suggests that several factors including micelle size and alkyl chain length need to be considered in the development of novel detergents for membrane protein research. Thus, this study not only describes new detergent tools potentially useful for membrane protein structural study, but also introduces plausible correlations between the chemical properties of detergents and membrane protein stabilization efficacy.

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Tandem neopentyl glycol maltosides (TNMs) for membrane protein stabilisation

Cited by 13 publications

References 41 publications

Structure–Function Relationships of Olfactory and Taste Receptors

Structure–Function Relationships of Olfactory and Taste Receptors

An Overview of the Top Ten Detergents Used for Membrane Protein Crystallization

Conformationally Restricted Monosaccharide-Cored Glycoside Amphiphiles: The Effect of Detergent Headgroup Variation on Membrane Protein Stability

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