| Download | - View final version: Structures and dynamics of native-state transmembrane protein targets and bound lipids (PDF, 4.3 MiB)
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| DOI | Resolve DOI: https://doi.org/10.3390/membranes11060451 |
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| Author | Search for: Overduin, MichaelORCID identifier: https://orcid.org/0000-0002-3114-6585; Search for: Trieber, CatharineORCID identifier: https://orcid.org/0000-0002-1336-1126; Search for: Prosser, R. Scott; Search for: Picard, Louis-Philippe; Search for: Sheff, Joey G.1 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Format | Text, Article |
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| Subject | drug discovery; GPCR; ion channel; native nanodisc; phosphoinositide; transmembrane protein; transporter |
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| Abstract | Membrane proteins work within asymmetric bilayers of lipid molecules that are critical for their biological structures, dynamics and interactions. These properties are lost when detergents dislodge lipids, ligands and subunits, but are maintained in native nanodiscs formed using styrene maleic acid (SMA) and diisobutylene maleic acid (DIBMA) copolymers. These amphipathic polymers allow extraction of multicomponent complexes of post-translationally modified membrane-bound proteins directly from organ homogenates or membranes from diverse types of cells and organelles. Here, we review the structures and mechanisms of transmembrane targets and their interactions with lipids including phosphoinositides (PIs), as resolved using nanodisc systems and methods including cryo-electron microscopy (cryo-EM) and X-ray diffraction (XRD). We focus on therapeutic targets including several G protein-coupled receptors (GPCRs), as well as ion channels and transporters that are driving the development of next-generation native nanodiscs. The design of new synthetic polymers and complementary biophysical tools bodes well for the future of drug discovery and structural biology of native membrane:protein assemblies (memteins). |
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| Publication date | 2021-06-17 |
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| Publisher | MDPI |
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| Licence | |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NRC number | NRC-HHT_53535A |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 26e15b4b-b521-47bb-b02f-0f0c7e284cff |
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| Record created | 2021-07-13 |
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| Record modified | 2021-07-13 |
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