Loop 3 of Short Neurotoxin II is an Additional Interaction Site with Membrane-bound Nicotinic Acetylcholine Receptor as Detected by Solid-state NMR Spectroscopy

Krabben, Ludwig; Rossum, Barth‐Jan van; Jehle, Stefan; Bocharov, Eduard V.; Lyukmanova, Ekaterina N.; Schulga, Alexey; Arseniev, Alexander S.; Hucho, Ferdinand; Oschkinat, Hartmut

doi:10.1016/j.jmb.2009.05.016

Cited by 26 publications

(16 citation statements)

References 49 publications

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“…Furthermore, isotopically labelled ligands have been studied when associated with non-labelled membrane receptors (Krabben et al, 2009;Luca et al, 2003;Williamson et al, 2002). Various MAS solid-state NMR techniques have also been applied to investigate the conformational properties, aggregation, peptide-lipid contacts and water accessibility of antimicrobial peptides when interacting with membranes, in particular several -sheet antimicrobial peptides have been characterized in this manner Tang and Hong, 2009).…”

Section: Solid-state Nmr Spectroscopy For the Investigations Of The Smentioning

confidence: 99%

The membrane interactions of antimicrobial peptides revealed by solid-state NMR spectroscopy

Bechinger

Salnikov

2012

Chemistry and Physics of Lipids

113

104

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Solid-state NMR spectroscopic techniques provide valuable information about the structure, dynamics and topology of membrane-inserted polypeptides. In particular antimicrobial peptides (or 'host defence peptides') have early on been investigated by solid-state NMR spectroscopy and many technical innovations in this domain have been developed with the help of these compounds when reconstituted into oriented phospholipid bilayers. Using solid-state NMR spectroscopy it could be shown for the first time that magainins or derivatives thereof exhibit potent antimicrobial activities when their cationic amphipathic helix is oriented parallel to the bilayer surface, a configuration found in later years for many other linear cationic amphipathic peptides. In contrast transmembrane alignments or lipid-dependent tilt angles have been found for more hydrophobic sequences such as alamethicin or β-hairpin antimicrobials. This review presents various solid-state NMR approaches and develops the basic underlying concept how angular information can be obtained from oriented samples. It is demonstrated how this information is used to calculate structures and topologies of peptides in their native liquid-disordered phospholipid bilayer environment. Special emphasis is given to discuss which NMR parameters provide the most complementary information, the minimal number of restraints needed and the effect of motions on the analysis of the NMR spectra. Furthermore, recent (31)P and (2)H solid-state NMR measurements of lipids are presented including some unpublished data which aim at investigating the morphological and structural changes of oriented or non-oriented phospholipids. Finally the structural models that have been proposed for the mechanisms of action of these peptides will be presented and discussed in view of the solid-state NMR and other biophysical experiments.

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Section: Solid-state Nmr Spectroscopy For the Investigations Of The Smentioning

confidence: 99%

The membrane interactions of antimicrobial peptides revealed by solid-state NMR spectroscopy

Bechinger

Salnikov

2012

Chemistry and Physics of Lipids

113

104

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“…[97] Different functional and ligand-binding states for natural and synthetic blockers have been probed using ssNMR spectroscopy. [54,96,121] Further studies on interactions between ligands and membrane proteins involved other ion channels [122] and G-proteincoupled receptors (GPCRs). [123] Many other membrane proteins have also been investigated using ssNMR spectroscopy, including membraneembedded enzymes, [49,98,124] histidine kinases, [29] ABC transporters, [125] and bacterial outer-membrane proteins.…”

Section: Membrane Proteinsmentioning

confidence: 99%

Solid‐State NMR Spectroscopy on Complex Biomolecules

2010

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Biomolecular applications of NMR spectroscopy are often merely associated with soluble molecules or magnetic resonance imaging. However, since the late 1970s, solid-state NMR (ssNMR) spectroscopy has demonstrated its ability to provide atomic-level insight into complex biomolecular systems ranging from lipid bilayers to complex biomaterials. In the last decade, progress in the areas of NMR spectroscopy, biophysics, and molecular biology have significantly expanded the repertoire of ssNMR spectroscopy for biomolecular studies. This Review discusses current approaches and methodological challenges, and highlights recent progress in using ssNMR spectroscopy at the interface of structural and cellular biology.

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“…Over the years, MAS NMR has elucidated details of membrane protein function including important studies of bacteriorhodopsin (Bajaj et al 2009; Mak-Jurkauskas et al 2008; Lansing et al 2002; Griffiths et al 2000b; Griffiths et al 2000a; Hatanaka et al 1999; Hu et al 1998; Lakshmi et al 1993; Thompson et al 1992; Harbison et al 1985; Ahuja et al 2009), potassium channels (Bhate and McDermott 2012; Bhate et al 2010; Schneider et al 2008b; Ader et al 2008; Lange et al 2006), the acetyl choline receptor (Williamson et al 1998; Williamson et al 2007; Krabben et al 2009), and a large number of applications are described in several recent reviews (Eddy and Yu 2014; McDermott 2009; McDermott 2004; Cross et al 2014; Hong et al 2012). Membrane protein structures have been determined from approaches combining MAS NMR spectroscopy with X-ray diffraction (Tang et al 2011), using oriented solid state NMR spectroscopy (Park et al 2012), and with solution NMR spectroscopy (Verardi et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR

Eddy

Silvers

et al. 2015

J Biomol NMR

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The human voltage dependent anion channel 1 (VDAC) is a 32 kDa β-barrel integral membrane protein that controls the transport of ions across the outer mitochondrial membrane. Despite the determination of VDAC solution and diffraction structures, a structural basis for the mechanism of its function is not yet fully understood. Biophysical studies suggest VDAC requires a lipid bilayer to achieve full function, motivating the need for atomic resolution structural information of VDAC in a membrane environment. Here we report an essential step toward that goal: extensive assignments of backbone and side chain resonances for VDAC in DMPC lipid bilayers via magic angle spinning nuclear magnetic resonance (MAS NMR). VDAC reconstituted into DMPC lipid bilayers spontaneously forms 2-dimensional lipid crystals, showing remarkable spectral resolution (0.5–0.3 ppm for 13C line width and less than 0.5 ppm 15N line widths at 750 MHz). In addition to the benefits of working in a lipid bilayer, several distinct advantages are observed with the lipid crystalline preparation. First, the strong signals and sharp line widths facilitated extensive NMR resonance assignments for an integral membrane β-barrel protein in lipid bilayers by MAS NMR. Second, a large number of residues in loop regions were readily observed and assigned, which can be challenging in detergent-solubilized membrane proteins where loop regions are often not detected due to line broadening from conformational exchange. Third, complete backbone and side chain chemical shift assignments could be obtained for the first 25 residues, which comprise the functionally important N-terminus. The reported assignments allow us to compare predicted torsion angles for VDAC prepared in DMPC 2D lipid crystals, DMPC liposomes, and LDAO-solubilized samples to address the possible effects of the membrane mimetic environment on the conformation of the protein. Concluding, we discuss the strengths and weaknesses of the reported assignment approach and the great potential for even more complete assignment studies and de novo structure determination via 1H detected MAS NMR.

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Loop 3 of Short Neurotoxin II is an Additional Interaction Site with Membrane-bound Nicotinic Acetylcholine Receptor as Detected by Solid-state NMR Spectroscopy

Cited by 26 publications

References 49 publications

The membrane interactions of antimicrobial peptides revealed by solid-state NMR spectroscopy

The membrane interactions of antimicrobial peptides revealed by solid-state NMR spectroscopy

Solid‐State NMR Spectroscopy on Complex Biomolecules

Lipid bilayer-bound conformation of an integral membrane beta barrel protein by multidimensional MAS NMR

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