Structures and dynamics of native-state transmembrane protein targets and bound lipids
| Autor: | Louis-Philippe Picard, Michael Overduin, R. Scott Prosser, Joey G. Sheff, Catharine A. Trieber |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Filtration and Separation TP1-1185 Review drug discovery 03 medical and health sciences Chemical engineering 0302 clinical medicine GPCR transmembrane protein Native state Chemical Engineering (miscellaneous) Nanodisc Ion channel G protein-coupled receptor Chemistry Chemical technology Process Chemistry and Technology native nanodisc Transmembrane protein phosphoinositide 030104 developmental biology Membrane Structural biology Membrane protein transporter ion channel Biophysics TP155-156 030217 neurology & neurosurgery |
| Zdroj: | Membranes Membranes, Vol 11, Iss 451, p 451 (2021) |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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