Conformations and Assembly of Amyloid Oligomers by Electrospray Ionisation - Ion Mobility Spectrometry - Mass Spectrometry

Illes‐Toth, Eva; Smith, David P.

doi:10.2174/157341113805218992

Cited by 2 publications

(2 citation statements)

References 102 publications

(232 reference statements)

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“…This shift to a more compact conformation on metal binding has also been observed by ESI-MS, where again an increased population of the compact state was observed on co-ordination of copper [19]. These results indicate that changes in solution condition leading to conformational change [12, 30–33] can be subsequently observed in the gas phase [34] and suggest a role for the collapsed partially folded state as the precursor to amyloid formation akin to other amyloid systems [35, 36]. …”

Section: Introductionmentioning

confidence: 72%

Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States

Illes‐Toth

Dalton

Smith

2013

J. Am. Soc. Mass Spectrom.

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Parkinson’s disease is the second most common neurodegenerative disorder, in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. α-Syn is known to be natively unstructured in equilibrium with subpopulations of more compact structures. It is these compact structures that are thought to be linked to amyloid formation. In the presence of DA, α-syn yields a diverse range of SDS-resistant, non-amyloid oligomers, however the precursor state conformation has not been established. Here, three DA molecules have been observed to bind per α-syn monomer by electrospray-ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS). Each of these DA molecules binds exclusively to the extended conformation of α-syn, and binding is not observed in the compact state of the protein. Measurements of collisional cross sectional areas show that the incremental uptake of DA pushes the protein towards a highly extended population, becoming fully populated upon the binding of three DA ligands. Tyrosine (Tyr) as a closely related structural analog, exhibited limited binding to the protein as compared with DA, with a maximum of two ligands being observed. Those Tyr ligands that do bind were observed as adducts to the extended conformation akin to DA. These findings suggest DA is able to modulate α-syn self-assembly by inducing the population of a highly extended state.FigureᅟElectronic supplementary materialThe online version of this article (doi:10.1007/s13361-013-0676-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 72%

Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States

Illes‐Toth

Dalton

Smith

2013

J. Am. Soc. Mass Spectrom.

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“…To overcome this, researchers turned to the use of ion mobility spectrometry (IMS), which can resolve the multimeric complex ions, not only by m/z, but also according to size based on their mobility in a drift tube [46][47][48]. In recent years, the combination of IMS with ESI MS has become an invaluable tool in deciphering the assembly mechanism of Aβ oligomers [31,47,[49][50][51][52][53]. While ESI IMS-MS is extremely powerful, the interpretation of two-dimensional data of drift time and m/z is not a straight forward task for multiply-charged homo-multi- The cells were incubated for 6, 24, 36, and 48 hours.…”

Section: Introductionmentioning

confidence: 99%

Detection of Amyloid Beta (Aβ) Oligomeric Composition Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS)

Wang

Whitehead

Yeung

2018

J. Am. Soc. Mass Spectrom.

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The use of MALDI MS as a fast and direct method to detect the Aβ oligomers of different masses is examined in this paper. Experimental results suggest that Aβ oligomers are ionized and detected as singly charged ions, and thus, the resulting mass spectrum directly reports the oligomer size distribution. Validation experiments were performed to verify the MS data against artifacts. Mass spectra collected from modified Aβ peptides with different propensities for aggregation were compared. Generally, the relative intensities of multimers were higher from samples where oligomerization was expected to be more favorable, and vice versa. MALDI MS was also able to detect the differences in oligomeric composition before and after the incubation/oligomerization step. Such differences in sample composition were also independently confirmed with an in vitro Aβ toxicity study on primary rat cortical neurons. An additional validation was accomplished through removal of oligomers from the sample using molecular weight cutoff filters; the resulting MS data correctly reflected the removal at the expected cutoff points. The results collectively validated the ability of MALDI MS to assess the monomeric/multimeric composition of Aβ samples. Graphical Abstract ᅟ.

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Conformations and Assembly of Amyloid Oligomers by Electrospray Ionisation - Ion Mobility Spectrometry - Mass Spectrometry

Cited by 2 publications

References 102 publications

Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States

Binding of Dopamine to Alpha-Synuclein is Mediated by Specific Conformational States

Detection of Amyloid Beta (Aβ) Oligomeric Composition Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS)

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