Measurement of peptide aggregation with pulsed-field gradient nuclear magnetic resonance spectroscopy

Mansfield, Shawn L; Jayawickrama, Dimuthu A.; Timmons, Jeffery S; Larive, Cynthia K.

doi:10.1016/s0167-4838(97)00162-3

Cited by 55 publications

(168 citation statements)

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“…There is a small contribution of PII at 0°C. Trying to break the structural states down into three different peptide segments, (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), (18)(19)(20)(21)(22)(23)(24), (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), we arrive at a simplified model with overall characteristics as described in Fig. 6.…”

Section: Structural Transitions Of Alzheimer B-peptidementioning

confidence: 99%

The Alzheimer β‐peptide shows temperature‐dependent transitions between left‐handed 3₁‐helix, β‐strand and random coil secondary structures

Danielsson¹,

Jarvet²,

Damberg³

et al. 2005

The FEBS Journal

123

149

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The temperature‐induced structural transitions of the full length Alzheimer amyloid β‐peptide [Aβ(1–40) peptide] and fragments of it were studied using CD and 1H NMR spectroscopy. The full length peptide undergoes an overall transition from a state with a prominent population of left‐handed 31 (polyproline II; PII)‐helix at 0 °C to a random coil state at 60 °C, with an average ΔH of 6.8 ± 1.4 kJ·mol−1 per residue, obtained by fitting a Zimm–Bragg model to the CD data. The transition is noncooperative for the shortest N‐terminal fragment Aβ(1–9) and weakly cooperative for Aβ(1–40) and the longer fragments. By analysing the temperature‐dependent 3JHNHα couplings and hydrodynamic radii obtained by NMR for Aβ(1–9) and Aβ(12–28), we found that the structure transition includes more than two states. The N‐terminal hydrophilic Aβ(1–9) populates PII‐like conformations at 0 °C, then when the temperature increases, conformations with dihedral angles moving towards β‐strand at 20 °C, and approaches random coil at 60 °C. The residues in the central hydrophobic (18–28) segment show varying behaviour, but there is a significant contribution of β‐strand‐like conformations at all temperatures below 20 °C. The C‐terminal (29–40) segment was not studied by NMR, but from CD difference spectra we concluded that it is mainly in a random coil conformation at all studied temperatures. These results on structural preferences and transitions of the segments in the monomeric form of Aβ may be related to the processes leading to the aggregation and formation of fibrils in the Alzheimer plaques.

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Section: Structural Transitions Of Alzheimer B-peptidementioning

confidence: 99%

The Alzheimer β‐peptide shows temperature‐dependent transitions between left‐handed 3₁‐helix, β‐strand and random coil secondary structures

Danielsson¹,

Jarvet²,

Damberg³

et al. 2005

The FEBS Journal

123

149

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“…As a technique for both biological and organic chemists, PFG NMR is extremely powerful as information regarding the diffusion of sample components can be acquired without chromatographic purification using standard NMR equipment. The use of this technique to study protein aggregation phenomenon has been demonstrated with a wide variety of biological systems (48)(49)(50). We chose to use this spectroscopic technique to monitor the interaction of nornicotine with A␤ as opposed to other techniques such as ultracentrifugation and dynamic light scattering as PFG-NMR allows direct measurements to be made rapidly on experimental samples, even with low-molecularweight samples not readily amenable to other techniques.…”

Section: Covalent Modification Of A␤ By Nornicotine and Inhibition Ofmentioning

confidence: 99%

Glycation of the amyloid β-protein by a nicotine metabolite: A fortuitous chemical dynamic between smoking and Alzheimer's disease

Dickerson

Janda²

2003

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

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The origin of Alzheimer's disease (AD) has been subjected to an intense amount of examination; however, a clear conclusion as to the nature of this crippling disease has yet to be identified. What is readily accepted is that a definitive marker of this disease is the aggregation of the amyloid ␤-peptide (A␤) into neuritic plaques. The recent observation that nicotine exposure leads to delayed onset of AD has stimulated a flurry of research into the nature of this neuroprotective effect. This phenomenon has been debated, but no consensus has been reached, and although these studies have targeted nicotine, the primary alkaloid in tobacco, few studies have considered the physiological role of nicotine metabolites in disease states. Nornicotine is a major nicotine metabolite in the CNS and has been shown to participate in the aberrant glycation of proteins in vivo in a process termed nornicotine-based glycation. Herein is detailed a potentially fortuitous role of nornicotine-based glycation in relation to the pathology of AD. Specifically, nornicotine was found to covalently alter A␤, leading to reduced peptide aggregation. Potential consequences of this reaction cascade include reduced plaque formation and͞or altered clearance of the peptide, as well as attenuated toxicity of soluble A␤ aggregates. The findings described provide an alternative mechanism for nicotine neuroprotection in AD and a means for the alteration of amyloid folding based on a covalent chemical event.

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“…15 The central hydrophobic region, residues 16-21, is crucial for theˇ-sheet forming oligomerization and subsequent fibril formation. 16 The N-terminus also shows some propensity to adopt an extendedˇ-strand with rising temperature. Raising the temperature even further induces a structural transition towards a random coil.…”

Section: Introductionmentioning

confidence: 99%

15N relaxation study of the amyloid β-peptide: structural propensities and persistence length

et al. 2006

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The dynamics of monomeric Alzheimer Abeta1-40 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 Abeta1-40 monomer was found to decrease from eight to three residues when temperature was increased from 3 to 18 degrees C. At 3 degrees 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 alpha-helical structure in membrane-mimicking systems. Our data leads to a structural model for the monomeric soluble beta-peptide with six different regions of secondary structure propensities. The peptide has two regions with beta-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.

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Measurement of peptide aggregation with pulsed-field gradient nuclear magnetic resonance spectroscopy

Cited by 55 publications

References 50 publications

The Alzheimer β‐peptide shows temperature‐dependent transitions between left‐handed 3₁‐helix, β‐strand and random coil secondary structures

The Alzheimer β‐peptide shows temperature‐dependent transitions between left‐handed 3₁‐helix, β‐strand and random coil secondary structures

Glycation of the amyloid β-protein by a nicotine metabolite: A fortuitous chemical dynamic between smoking and Alzheimer's disease

15N relaxation study of the amyloid β-peptide: structural propensities and persistence length

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Measurement of peptide aggregation with pulsed-field gradient nuclear magnetic resonance spectroscopy

Cited by 55 publications

References 50 publications

The Alzheimer β‐peptide shows temperature‐dependent transitions between left‐handed 31‐helix, β‐strand and random coil secondary structures

The Alzheimer β‐peptide shows temperature‐dependent transitions between left‐handed 31‐helix, β‐strand and random coil secondary structures

Glycation of the amyloid β-protein by a nicotine metabolite: A fortuitous chemical dynamic between smoking and Alzheimer's disease

15N relaxation study of the amyloid β-peptide: structural propensities and persistence length

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The Alzheimer β‐peptide shows temperature‐dependent transitions between left‐handed 3₁‐helix, β‐strand and random coil secondary structures

The Alzheimer β‐peptide shows temperature‐dependent transitions between left‐handed 3₁‐helix, β‐strand and random coil secondary structures