Phospholipid phase transitions in homogeneous nanometer scale bilayer discs

Shaw, Andrew; McLean, Mark A.; Sligar, Stephen G.

doi:10.1016/s0014-5793(03)01400-5

Cited by 132 publications

(164 citation statements)

References 26 publications

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“…Disk-to-vesicle conversion was also evident from the DSC data recorded in repetitive scans of the same sample (Fig. 3B, solid and dashed lines): the fi rst heating scan showed a relatively broad gelto-liquid crystal phase transition centered at 26°C, which is characteristic of discoidal rHDL, whereas the second scan showed a sharper transition (refl ecting larger cooperative unit) that was shifted to T c = 24°C, which is characteristic of DMPC vesicles ( 47 ). Furthermore, compared with the fi rst heating scan, consecutive heating scans monitored by DSC and CD resulted in lower apparent melting temperature T m (Fig.…”

Section: Effects Of Cholesterol On the Structure And Stability Of Apomentioning

confidence: 71%

Effects of cholesterol on thermal stability of discoidal high density lipoproteins

Jayaraman

Benjwal

Gantz

et al. 2010

Journal of Lipid Research

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Section: Effects Of Cholesterol On the Structure And Stability Of Apomentioning

confidence: 71%

Effects of cholesterol on thermal stability of discoidal high density lipoproteins

Jayaraman

Benjwal

Gantz

et al. 2010

Journal of Lipid Research

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“…The lipid composition is also tuneable because it is possible to add cholesterol and/or charged lipids 17. Lipid physical properties in nanodiscs have been studied and compared with existing membrane models by different biophysical techniques, such as small‐angle X‐ray scattering (SAXS),9, 10, 35, 40 small‐angle neutron scattering (SANS),35, 41 NMR spectroscopy31, 34 or fluorescence spectroscopy 35, 39. Although a general consensus concerning the driving force of nanodisc assembly and the resulting MSP architecture exists nowadays,5, 11 little is known about the internal dynamics of lipids and membrane proteins embedded in nanodiscs, as well as how the lipid–lipid and lipid–protein dynamic interplay influence the membrane protein activity.…”

Section: Introductionmentioning

confidence: 99%

Lipid Internal Dynamics Probed in Nanodiscs

et al. 2017

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Nanodiscs offer a very promising tool to incorporate membrane proteins into native‐like lipid bilayers and an alternative to liposomes to maintain protein functions and protein–lipid interactions in a soluble nanoscale object. The activity of the incorporated membrane protein appears to be correlated to its dynamics in the lipid bilayer and by protein–lipid interactions. These two parameters depend on the lipid internal dynamics surrounded by the lipid‐encircling discoidal scaffold protein that might differ from more unrestricted lipid bilayers observed in vesicles or cellular extracts. A solid‐state NMR spectroscopy investigation of lipid internal dynamics and thermotropism in nanodiscs is reported. The gel‐to‐fluid phase transition is almost abolished for nanodiscs, which maintain lipid fluid properties for a large temperature range. The addition of cholesterol allows fine‐tuning of the internal bilayer dynamics by increasing chain ordering. Increased site‐specific order parameters along the acyl chain reflect a higher internal ordering in nanodiscs compared with liposomes at room temperature; this is induced by the scaffold protein, which restricts lipid diffusion in the nanodisc area.

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“…It was recently reported that reconstituted high-density lipoproteins (rHDLs), which are also known as nanodiscs (29), can accommodate membrane proteins within a 10-nm-diameter diskshaped lipid bilayer (30). The rHDLs reportedly provide a lipid environment with more native-like properties, compared with liposomes, in terms of the lateral pressure and curvature profiles because detergent micelles have strong curvature and different lateral pressure profiles from lipid membranes (31). Our NMR analyses of a G protein-coupled receptor (GPCR) and an ion channel in rHDL lipid bilayers revealed that the population and the exchange rates of the conformational equilibrium determine their signal transduction and ion transport activities (32)(33)(34) and that the population of the active conformation of the GPCR in rHDLs correlated better with the signaling levels than that in detergent micelles (32).…”

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confidence: 99%

Conductance of P2X ₄ purinergic receptor is determined by conformational equilibrium in the transmembrane region

Minato

Suzuki

Hara

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Ligand-gated ion channels are partially activated by their ligands, resulting in currents lower than the currents evoked by the physiological full agonists. In the case of P2X purinergic receptors, a cationselective pore in the transmembrane region expands upon ATP binding to the extracellular ATP-binding site, and the currents evoked by α,β-methylene ATP are lower than the currents evoked by ATP. However, the mechanism underlying the partial activation of the P2X receptors is unknown although the crystal structures of zebrafish P2X 4 receptor in the apo and ATP-bound states are available. Here, we observed the NMR signals from M339 and M351, which were introduced in the transmembrane region, and the endogenous alanine and methionine residues of the zebrafish P2X 4 purinergic receptor in the apo, ATP-bound, and α,β-methylene ATP-bound states. Our NMR analyses revealed that, in the α,β-methylene ATP-bound state, M339, M351, and the residues that connect the ATP-binding site and the transmembrane region, M325 and A330, exist in conformational equilibrium between closed and open conformations, with slower exchange rates than the chemical shift difference (<100 s −1 ), suggesting that the small population of the open conformation causes the partial activation in this state. Our NMR analyses also revealed that the transmembrane region adopts the open conformation in the state bound to the inhibitor trinitrophenyl-ATP, and thus the antagonism is due to the closure of ion pathways, except for the pore in the transmembrane region: i.e., the lateral cation access in the extracellular region.NMR | membrane proteins | ligand-gated ion channels | insect cell expression system | purinergic receptors I n chemical neurotransmission, various neurotransmitters bind to ligand-gated ion channels expressed in the plasma membrane of postsynaptic cells, such as the NMDA, AMPA, and P2X receptors, leading to changes in membrane potential and the concentration of intracellular ions. Each ligand for a ligand-gated ion channel has a distinct ability to evoke currents (1), and the ligands are classified according to the evoked current level: such as, full agonists, partial agonists, and antagonists. Partial agonists of ligand-gated ion channels reportedly offer clinical advantages over antagonists and full agonists in antidepressant and smoking-cessation treatment (2, 3).Two mechanisms have been proposed for the partial activation of the ligand-gated ion channels: the equilibrium between the open and closed conformations and the distinct conformation of the partial agonist-bound states from the closed and open conformations (4, 5). In the crystal structures of the extracellular region of the AMPA receptor, in which the distances between the two extracellular domains are changed upon agonist binding, the interdomain distances in the partial agonist-bound states correlated with the conductance level, suggesting that the AMPA receptor adopts specific intermediately permeable conformations (4, 6).The P2X receptors are a family of cation channe...

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Phospholipid phase transitions in homogeneous nanometer scale bilayer discs

Cited by 132 publications

References 26 publications

Effects of cholesterol on thermal stability of discoidal high density lipoproteins

Effects of cholesterol on thermal stability of discoidal high density lipoproteins

Lipid Internal Dynamics Probed in Nanodiscs

Conductance of P2X ₄ purinergic receptor is determined by conformational equilibrium in the transmembrane region

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Phospholipid phase transitions in homogeneous nanometer scale bilayer discs

Cited by 132 publications

References 26 publications

Effects of cholesterol on thermal stability of discoidal high density lipoproteins

Effects of cholesterol on thermal stability of discoidal high density lipoproteins

Lipid Internal Dynamics Probed in Nanodiscs

Conductance of P2X 4 purinergic receptor is determined by conformational equilibrium in the transmembrane region

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Conductance of P2X ₄ purinergic receptor is determined by conformational equilibrium in the transmembrane region