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- Danielsson, J, et al.
(författare)
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15N relaxation study of the amyloid beta-peptide structural propensities and persistence length.
- 2006
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Ingår i: Magn Reson Chem. - : Wiley. - 0749-1581. ; 44:S1, s. S114-21
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Tidskriftsartikel (refereegranskat)abstract
- The dynamics of monomeric Alzheimer A(1-40) in aqueous solution was studied using heteronuclear NMR experiments. 15N NMR relaxation rates of amide groups report on the dynamics in the peptide chain and make it possible to estimate structural propensities from temperature-dependent relaxation data and chemical shifts change analysis. The persistence length of the polypeptide chain was determined using a model in which the influence of neighboring residue relaxation is assumed to decay exponentially as a function of distance. The persistence length of the A(1-40) monomer was found to decrease from eight to three residues when temperature was increased from 3 to 18 °C. At 3 °C the peptide shows structural propensities that correlate well with the suggested secondary structure regions of the peptide to be present in the fibrils, and with the -helical structure in membrane-mimicking systems. Our data leads to a structural model for the monomeric soluble -peptide with six different regions of secondary structure propensities. The peptide has two regions with -strand propensity (residues 16-24 and 31-40), two regions with high PII-helix propensity (residues 1-4 and 11-15) and two unstructured regions with higher mobility (residues 5-10 and 25-30) connecting the structural elements. Copyright © 2006 John Wiley & Sons, Ltd.
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- Blom, A M, et al.
(författare)
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Structural characterization of inter-alpha-inhibitor. Evidence for an extended shape
- 1999
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 274:1, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- Inter-alpha-inhibitor (IalphaI) is a 180-kDa serum protein consisting of three polypeptides. Two of these, the heavy chains 1 and 2 (H1 and H2), are of 75-80 kDa and have similar amino acid sequences. The third polypeptide, bikunin, has a molecular mass of 25 kDa and contains a 7-kDa chondroitin sulfate chain that is covalently linked to the C-terminal amino acid residues of H1 and H2. IalphaI has been shown to be required for the formation of the hyaluronan-containing extracellular matrix of certain cell types. How IalphaI exerts this function is not known, but it appears that upon interaction with cells, the heavy chains are released and become covalently linked to hyaluronan. Our results indicate that IalphaI and its heavy chains are extended molecules; thus, upon electron microscopy, IalphaI appeared to consist of two globular domains connected by a thin structure 31-nm long and the isolated heavy chains of a globular domain and a "tail" about 15-nm long. Analysis of the heavy chains by partial proteolysis showed that the C-terminal halves are particularly sensitive to hydrolysis indicating that they are loosely folded. Furthermore, electron microscopy showed that partially degraded heavy chains lacked the extended regions. Taken together, these results suggest that the N-terminal half of the heavy chains forms a globular domain, whereas the other half has an extended and loosely folded structure.
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| 20. |
- Lindskog, M, et al.
(författare)
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Monitoring intracellular metabolites in neuroblastoma with 1H NMR spectroscopy: effects of growth factor withdrawal and modulation of lipid metabolism
- 2004
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Ingår i: SPECTROSCOPY-AN INTERNATIONAL JOURNAL. - : Hindawi Limited. - 0712-4813. ; 18:2, s. 123-132
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 1H NMR spectroscopy has previously been employed to detect and monitor changes in the lipid metabolism of neuroblastoma cells upon cytotoxic treatment. Here, we addressed the question whether altered growth conditions, by presence or absence of serum, would impact on the metabolites detectable with1H NMR spectroscopy. Chronic serum deprivation of SH‒SY5Y human neuroblastoma cells resulted in a decrease in the intracellular content of several metabolites, in particular total choline. This metabolic effect was paralleled by significant growth inhibition. In addition, we investigated the potential functional origin of intracellular1H NMR visible lipids in SH‒SY5Y cells. A drop in lipid methylene protons could be observed shortly after serum‒withdrawal. Contrary, removal of lipoproteins from the serum led to a pronounced increase in intracellular lipids, as did inhibition of de novo sterol synthesis by lovastatin. In conclusion, we demonstrate that intracellular total choline in neuroblastoma cells in vitro is highly dependent on the availability of growth factors. Furthermore, we show that1H NMR visible lipids decrease upon serum‒withdrawal but are accumulated when cholesterol supply is abrogated. The biological and potential clinical implications of these findings are discussed.
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| 23. |
- Papadopoulos, E, et al.
(författare)
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NMR solution structure of the peptide fragment 1-30, derived from unprocessed mouse Doppel protein, in DHPC micelles.
- 2006
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 45:1, s. 159-66
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Tidskriftsartikel (refereegranskat)abstract
- The downstream prion-like Doppel (Dpl) protein is a homologue related to the prion protein (PrP). Dpl is expressed in the brains of mice that do not express PrP, and Dpl is known to be toxic to neurons. One mode of toxicity has been suggested to involve direct membrane interactions. PrP under certain conditions of cell trafficking retains an uncleaved signal peptide, which may also hold for the much less studied Dpl. For a peptide with a sequence derived from the N-terminal part (1-30) of mouse Dpl (mDpl(1-30)) CD spectroscopy shows about 40% alpha-helical structure in DHPC and SDS micelles. In aqueous solution it is mostly a random coil. The three-dimensional solution structure was determined by NMR for mDpl(1-30) associated with DHPC micelles. 2D 1H NMR spectra of the peptide in q = 0.25 DMPC/DHPC bicelles only showed signals from the unstructured termini, indicating that the structured part of the peptide resides within the lipid bilayer. Together with 2H2O exchange data in the DHPC micelle solvent, these results show an alpha-helix protected from solvent exchange between residues 7 and 19, and suggest that the alpha-helical segment can adopt a transmembrane localization also in a membrane. Leakage studies with entrapped calcein in large unilamellar phospholipid vesicles showed that the peptide is almost as membrane perturbing as melittin, known to form pores in membranes. The results suggest a possible channel formation mechanism for the unprocessed Dpl protein, which may be related to toxicity through direct cell membrane interaction and damage.
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