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

Wang, Jasmine S.-H.; Whitehead, Shawn N.; Yeung, Ken K.‐C.

doi:10.1007/s13361-018-1896-z

Cited by 19 publications

(14 citation statements)

References 66 publications

(68 reference statements)

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“…In general, the combined study presented here is representative of a growing body of work that utilizes native MS with a goal of elucidating protein interactions with lipid membranes as well as the effect of such interactions upon biomolecular structure . Additionally, the work becomes part of a larger body of studies aimed at determining the mechanisms of aggregation for pathologically‐relevant proteins …”

Section: Introductionmentioning

confidence: 99%

Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics

et al. 2019

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The first 17 amino acid residues of Huntingtin protein (Nt17 of htt) are thought to play an important role in the protein's function; Nt17 is one of two membrane binding domains in htt. In this study the binding ability of Nt17 peptide with vesicles comprised of two subclasses of phospholipids is studied using electrospray ionization -mass spectrometry (ESI-MS) and molecular dynamics (MD) simulations. Overall, the peptide is shown to have a greater propensity to interact with vesicles of phosphatidylcholine (PC) rather than phosphatidylethanolamine (PE) lipids. Mass spectra show an increase in lipid-bound peptide adducts where the ordering of the number of such specie is 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) > 1-palmitoyl-2-oleoylglycero-3-phosphocholine (POPC) > 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphoethanolamine (POPE). MD simulations suggest that the compactness of the bilayer plays a role in governing peptide interactions. The peptide shows greater disruption of the DOPC bilayer order at the surface and interacts with the hydrophobic tails of lipid molecules via hydrophobic residues. Conversely, the POPE vesicle remains ordered and lipids display transient interactions with the peptide through the formation of hydrogen bonds with hydrophilic residues. The POPC system displays intermediate behavior with regard to the degree of peptide-membrane interaction. Finally, the simulations suggest a helix stabilizing effect resulting from the interactions between hydrophobic residues and the lipid tails of the DOPC bilayer. K E Y W O R D S peptide interactions, native MS, molecular dynamics simulations, Huntingtin, Protein aggregation

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Section: Introductionmentioning

confidence: 99%

Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics

et al. 2019

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“…Like complex-up and complex -down, this method relies on native (electrospray) ionization of monomeric proteins and noncovalent assemblies (although reports of ionization of intact peptide oligomers and protein complexes using MALDI have recently been published [38, 39]). In contrast to the aforementioned methods, the higher order structure is largely assumed to be retained during backbone cleavage in native top-down (nTD) experiments.…”

Section: Proposed New and Updated Terminology For Top-down Experimentsmentioning

confidence: 99%

Top or Middle? Up or Down? Toward a Standard Lexicon for Protein Top-Down and Allied Mass Spectrometry Approaches

Lermyte

Tsybin

O’Connor

et al. 2019

J. Am. Soc. Mass Spectrom.

106

114

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In recent years, there has been increasing interest in top-down mass spectrometry (TDMS) approaches for protein analysis, driven both by technological advancements and efforts such as those by the multinational Consortium for Top-Down Proteomics (CTDP). Today, diverse sample preparation and ionization methods are employed to facilitate TDMS analysis of denatured and native proteins and their complexes. The goals of these studies vary, ranging from protein and proteoform identification, to determination of the binding site of a (non)covalently-bound ligand, and in some cases even with the aim to study the higher order structure of proteins and complexes. Currently, however, no widely accepted terminology exists to precisely and unambiguously distinguish between the different types of TDMS experiments that can be performed. Instead, ad hoc developed terminology is often used, which potentially complicates communication of top-down and allied methods and their results. In this communication, we consider the different types of top-down (or top-down-related) MS experiments that have been performed and reported, and define distinct categories based on the protocol used and type(s) of information that can be obtained. We also consider the different possible conventions for distinguishing between middle- and top-down MS, based on both sample preparation and precursor ion mass. We believe that the proposed framework presented here will prove helpful for researchers to communicate about TDMS and will be an important step toward harmonizing and standardizing this growing field. Graphical Abstract

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“…However, it is worth noting that ESI-MALDI is not a fully quantitative analysis tool and rather produces a more qualitative result. Regardless of that, ESI-MALDI could be a powerful method allowing researchers to confirm the Aβ species and aggregates produced during their experimental design (Wang et al, 2018). Fiori et al (2013) utilised both ESI-ion trap-MS, as well as MALDI-TOF-MS to gain a comprehensive insight into the aggregation of Aβ25-35 peptide fragment.…”

Section: Mass Spectrometrymentioning

confidence: 99%

Biological and methodological complexities of beta‐amyloid peptide: Implications for Alzheimer’s disease research

Matuszyk

Garwood

Ferraiuolo

et al. 2021

Journal of Neurochemistry

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Although controversial, the amyloid cascade hypothesis remains central to the Alzheimer's disease (AD) field and posits amyloid‐beta (Aβ) as the central factor initiating disease onset. In recent years, there has been an increase in emphasis on studying the role of low molecular weight aggregates, such as oligomers, which are suggested to be more neurotoxic than fibrillary Aβ. Other Aβ isoforms, such as truncated Aβ, have also been implicated in disease. However, developing a clear understanding of AD pathogenesis has been hampered by the complexity of Aβ biochemistry in vitro and in vivo. This review explores factors contributing to the lack of consistency in experimental approaches taken to model Aβ aggregation and toxicity and provides an overview of the different techniques available to analyse Aβ, such as electron and atomic force microscopy, nuclear magnetic resonance spectroscopy, dye‐based assays, size exclusion chromatography, mass spectrometry and SDS‐PAGE. The review also explores how different types of Aβ can influence Aβ aggregation and toxicity, leading to variation in experimental outcomes, further highlighting the need for standardisation in Aβ preparations and methods used in current research.

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

Cited by 19 publications

References 66 publications

Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics

Investigating the interactions of the first 17 amino acid residues of Huntingtin with lipid vesicles using mass spectrometry and molecular dynamics

Top or Middle? Up or Down? Toward a Standard Lexicon for Protein Top-Down and Allied Mass Spectrometry Approaches

Biological and methodological complexities of beta‐amyloid peptide: Implications for Alzheimer’s disease research

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