Recoupled separated-local-field experiments and applications to study intermediate-regime molecular motions

Cobo, Marcio Fernando; Achilles, Anja; Reichert, Detlef; deAzevedo, Eduardo R.; Saalwächter, Kay

doi:10.1016/j.jmr.2012.05.003

Cited by 23 publications

(32 citation statements)

References 33 publications

(61 reference statements)

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“…In a lamellar gel phase, the acyl chains adopt an all-trans (AT) conformation (33) and have reorientation motions with timescales near microseconds (34), the so-called intermediate regime motions in NMR spectroscopy (35). The intermediateregime motions cause a severe broadening of the 13 C NMR peaks as confirmed by the DP-CP-rINEPT spectra of a DPPC lamellar gel phase, L β , shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Andersson

Grey

Larsson

et al. 2017

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

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The lipid-protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant extract using a multitechnique approach consisting of 1 H-13 C solid-state nuclear magnetic spectroscopy, small-and wide-angle X-ray scattering, and mass spectrometry. The detailed characterization presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant, the surfactant extract adopts a single liquid-ordered lamellar phase, L α(o) , at physiological temperatures. This L α(o) phase gradually changes into a liquid-disordered lamellar phase, L α(d) , when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and one L α(d) phase. Remarkably, it was possible to measure a large set of order parameter magnitudes |S CH | from the liquiddisordered and -ordered lamellar phases and assign them to specific C-H bonds of the phospholipids in the biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic the physiological selfassembly compositions for treatment of pathological states such as respiratory distress syndrome.T he air-alveoli interface of human lungs consists of ∼100 m 2 of surface area covered by a 1-to 2-µm-thick film rich in lipids, generally referred to as lung surfactant (LS) (1, 2). The alveolar interfacial film has several important functions, including stabilizing the interface, allowing for area expansions and controlling diffusional transport (3-7). These functions strongly rely on the self-assembly structure, as well as on the mechanical, barrier, and surface properties of the dynamic LS interfacial layer, which in turn depend on its chemical composition and external conditions in terms of compression, hydration, and so on. The main components of LS are phospholipids, cholesterol, and the so-called surfactant proteins representing ∼80, 10, and 10 wt %, respectively (2).Deficiency of LS in the alveoli, or an imbalance of its chemical composition, induces a number of pathological conditions (8). For instance, neonatal respiratory distress syndrome affects prematurely born infants when LS is not yet matured or is completely lacking; this deficiency may be lethal if left untreated. In these cases, the most common treatment is intratracheal administration of an exogenous LS into the lungs (9). In case of acute respiratory distress syndrome the mortality is 35 to 45% (10) and an effective treatment is clearly lacking (8). An accurate characterization of the molecular structure and dynamics of endogenous an...

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Section: Resultsmentioning

confidence: 99%

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Andersson

Grey

Larsson

et al. 2017

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

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“…Interestingly, Osaka DMSO and wild-type Aβ40 exhibit similar order parameters that are smaller than the Arctic Aβ40 S CH values for both the backbone and sidechains. However, the Arctic sample exhibits larger intensity asymmetry in the dipolar oscillation, indicating more pronounced microsecond timescale motion 71,72 .…”

Section: Resultsmentioning

confidence: 99%

Structural Polymorphism of Alzheimer’s β-Amyloid Fibrils as Controlled by an E22 Switch: A Solid-State NMR Study

et al. 2016

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The amyloid-β (Aβ) peptide of Alzheimer’s disease (AD) forms polymorphic fibrils on the micrometer scale and molecular scale. Various fibril growth conditions have been identified to cause polymorphism, but the intrinsic amino acid sequence basis for this polymorphism has been unclear. Several single-site mutations in the center of the Aβ sequence cause different disease phenotypes and fibrillization properties. The E22G (Arctic) mutant is found in familial AD and forms protofibrils more rapidly than wild-type Aβ. Here, we use solid-state NMR spectroscopy to investigate the structure, dynamics, hydration and morphology of Arctic E22G Aβ40 fibrils. 13C, 15N-labeled synthetic E22G Aβ40 peptides are studied and compared with wild-type and Osaka E22Δ Aβ40 fibrils. Under the same fibrillization conditions, Arctic Aβ40 exhibits a high degree of polymorphism, showing at least four sets of NMR chemical shifts for various residues, while the Osaka and wild-type Aβ40 fibrils show a single or a predominant set of chemical shifts. Thus, structural polymorphism is intrinsic to the Arctic E22G Aβ40 sequence. Chemical shifts and inter-residue contacts obtained from 2D correlation spectra indicate that one of the major Arctic conformers has surprisingly high structural similarity with wild-type Aβ42. 13C-1H dipolar order parameters, 1H rotating-frame spin-lattice relaxation times and water-to-protein spin diffusion experiments reveal substantial differences in the dynamics and hydration of Arctic, Osaka and wild-type Aβ40 fibrils. Together, these results strongly suggest that electrostatic interactions in the center of the Aβ peptide sequence play a crucial role in the three-dimensional fold of the fibrils, and by inference, fibril-induced neuronal toxicity and AD pathogenesis.

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“…Thus, for a smaller interaction strength the interaction is averaged up to longer time scales. Experimental approaches to characterizing this intermediate regime have been discussed [150,151].…”

Section: Measurements Of Anisotropic Interactions Under Mas Can Be Domentioning

confidence: 99%

Studying dynamics by magic-angle spinning solid-state NMR spectroscopy: Principles and applications to biomolecules

Schanda

Ernst

2016

Progress in Nuclear Magnetic Resonance Spectroscopy

198

295

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Magic-angle spinning solid-state NMR spectroscopy is an important technique to study molecular structure, dynamics and interactions, and is rapidly gaining importance in biomolecular sciences. Here we provide an overview of experimental approaches to study molecular dynamics by MAS solid-state NMR, with an emphasis on the underlying theoretical concepts and differences of MAS solid-state NMR compared to solution-state NMR. The theoretical foundations of nuclear spin relaxation are revisited, focusing on the particularities of spin relaxation in solid samples under magic-angle spinning. We discuss the range of validity of Redfield theory, as well as the inherent multi-exponential behavior of relaxation in solids. Experimental challenges for measuring relaxation parameters in MAS solid-state NMR and a few recently proposed relaxation approaches are discussed, which provide information about time scales and amplitudes of motions ranging from picoseconds to milliseconds. We also discuss the theoretical basis and experimental measurements of anisotropic interactions (chemical-shift anisotropies, dipolar and quadrupolar couplings), which give direct information about the amplitude of motions. The potential of combining relaxation data with such measurements of dynamically-averaged anisotropic interactions is discussed. Although the focus of this review is on the theoretical foundations of dynamics studies rather than their application, we close by discussing a small number of recent dynamics studies, where the dynamic properties of proteins in crystals are compared to those in solution.

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Recoupled separated-local-field experiments and applications to study intermediate-regime molecular motions

Cited by 23 publications

References 33 publications

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract

Structural Polymorphism of Alzheimer’s β-Amyloid Fibrils as Controlled by an E22 Switch: A Solid-State NMR Study

Studying dynamics by magic-angle spinning solid-state NMR spectroscopy: Principles and applications to biomolecules

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