Role of Bilayer Characteristics on the Structural Fate of Aβ(1–40) and Aβ(25–40)

Xiong, Jian; Roach, Carol A.; Oshokoya, Olayinka O.; Schroell, Robert P.; Yakubu, Rauta A.; Eagleburger, Michael K.; Cooley, Jason W.; JiJi, Renee D.

doi:10.1021/bi4016296

Cited by 10 publications

(10 citation statements)

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“…From Figure 5, it is apparent that fibrils can be formed at lipid surfaces at low Aβ concentration in the presence of Ca 2+ , and the fibril-accelerated conversion of monomers into cytotoxic oligomers can ultimately lead to membrane damage. 9 Recently, Xiong et al 82 suggest that insertion of Aβ(1−40) into lipid bilayers is followed by a conversion into the β-sheet structure, which forces the Cterminus out of the membrane for incorporating additional Aβ(1−40) molecules. However, in the presence of Ca 2+ , the Cterminus is stabilized and does not need to insert into the lipids to maximize the hydrophobic interaction or decrease the electrostatic repulsion.…”

Section: ■ Discussionmentioning

confidence: 99%

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Zhang

Gong

et al. 2015

Biochemistry

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The amyloid cascade hypothesis links the amyloid-β (Aβ) peptide aggregation to neuronal cell damage and ultimately the etiology of Alzheimer's disease (AD). Although Aβ aggregation has been known to accelerate at cell membranes, the exact mechanism of Aβ peptide deposition and the involvement of extracellular species are still largely unclear. Using surface plasmon resonance (SPR) and atomic force microscopy (AFM), we demonstrate that Ca(2+) ions, in conjunction with lipid bilayer, lower the threshold concentration for Aβ aggregation (>a few micromolar in vitro) to physiological levels (low nanomolar). Circular dichroism spectroscopy reveals that Ca(2+) ions and the lipid bilayer concertedly accelerate the conformational change or misfolding of Aβ peptides. Molecular dynamics calculation indicates that Ca(2+) is sandwiched between Glu-22 of Aβ and the lipid phosphate group. SPR experiments conducted using an E22G mutant confirmed the strong interaction among Ca(2+), Aβ(1-42), and the phospholipid bilayer. With the C- and N-termini of the Aβ dimer fully exposed for the attachment of additional Aβ molecules, fibrils formed with the Ca(2+)-anchored Aβ nuclei appear to interact with lipid bilayers differently from those preformed in solution. Thus, similar to the role of Ca(2+) in enriching islet amyloid polypeptides in the pancreas of diabetic patients ( Biophys. J. 2013 , 104 , 173 - 184 ) and the "Ca(2+) bridge" in mediating membrane interaction with α-synuclein in the Parkinson's disease ( Biochemistry , 2006 , 45 , 10947 - 10956 ), the influence of Ca(2+) on the Aβ adsorption at cell membranes, which leads to neuronal membrane damage in AD, cannot be overlooked.

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Section: ■ Discussionmentioning

confidence: 99%

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Zhang

Gong

et al. 2015

Biochemistry

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“…601 Aβ40 also behaved similarly to strongly adsorbed on anionic DLPG liposomes, with spontaneous structural transition from where it initially adopts mixtures of disordered and helical structures. 602 Furthermore, increased cholesterol in POPC bilayer promoted Aβ42 monomer with different conformations (i.e. α-helical and β-hairpin) to be adsorbed on the POPC bilayer, which further facilitated Aβ aggregation and membrane insertion (Figure 19d).…”

Section: Aβ40/42 and Its Mutantsmentioning

confidence: 99%

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

et al. 2021

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Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D) and amyotrophic lateral sclerosis (ALS) research, respectively for over many years.While SOD1 is a globular protein with a well-defined 3D structure, the Aβ, tau and α-synuclein proteins belong to the class of intrinsically disordered proteins (IDPs). IDPs are also known to play a critical role in many cellular functions such as signal transduction, cell growth, binding with DNA and RNA, and transcription, and are implicated in the development of cardiovascular problems and cancers 29 . The IDPs involved in neurodegenerative diseases have a few aggregation-prone regions and overall all IDPs have a low mean hydrophobicity and a high mean net charge 30 .IDPs are structurally flexible and lack stable secondary structures in aqueous solution. When isolated, they behave as polymers in a good solvent and their radii of gyration are well described by the Flory scaling law. 31 The insolubility and high self-assembly propensity of IDPs implicated in degenerative diseases have prevented high-resolution structural determination by solution nuclear magnetic resolution (NMR) and X-ray diffraction experiments. Local information at all aggregation steps can be, however, obtained by chemical shifts, residual coupling constants, and J-couplings from NMR, exchange hydrogen/deuterium (H/D) NMR, Raman spectroscopy; and secondary structure from fast Fourier infrared spectroscopy (FTIR) or circular dichroism (CD). Long-range tertiary contacts can be deduced from paramagnetic relaxation enhancement (PRE) NMR spectroscopy and single molecule Förster resonance energy transfer (sm-FRET), and short-range distance contacts can be extracted by cross linked residues determined by mass spectrometry (MS). Low-resolution 3D information of monomers and oligomers can be obtained by ion-mobility mass-spectrometry data (IM/MS) providing cross-collision sections, dynamic light scattering (DLS), pulse field gradient NMR spectroscopy and fluorescence correlation spectroscopy (FCS) providing hydrodynamics radius, small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), atomic force microscopy (AFM) and transmission electron microscopy (TEM) providing height features of the aggregates, as reported by some o...

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“…It was found that the peptide initially adopts mixtures of disordered and helical structures upon the interaction with anionic liposomes, which is followed by their conversion into β-sheet over longer timeframes. 71 …”

Section: Early Stages In Protein Aggregation Detection Of Prefibrilamentioning

confidence: 99%

Exploring the structure and formation mechanism of amyloid fibrils by Raman spectroscopy: a review

Kurouski

Duyne

Lednev

2015

Analyst

229

200

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Amyloid fibrils are β-sheet rich protein aggregates that are strongly associated with various neurodegenerative diseases. Raman spectroscopy has been broadly utilized to investigate protein aggregation and amyloid fibril formation and has been shown to be capable of revealing changes in secondary and tertiary structures at all stages of fibrillation. When coupled with atomic force (AFM) and scanning electron (SEM) microscopies, Raman spectroscopy becomes a powerful spectroscopic approach that can investigate the structural organization of amyloid fibril polymorphs. In this review, we discuss the applications of Raman spectroscopy, a unique, label-free and non-destructive technique for the structural characterization of amyloidogenic proteins, prefibrilar oligomers, and mature fibrils.

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Role of Bilayer Characteristics on the Structural Fate of Aβ(1–40) and Aβ(25–40)

Cited by 10 publications

References 50 publications

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

Exploring the structure and formation mechanism of amyloid fibrils by Raman spectroscopy: a review

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Role of Bilayer Characteristics on the Structural Fate of Aβ(1–40) and Aβ(25–40)

Cited by 10 publications

References 50 publications

Ca2+ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Ca2+ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

Exploring the structure and formation mechanism of amyloid fibrils by Raman spectroscopy: a review

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Product

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Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration

Ca²⁺ Interacts with Glu-22 of Aβ(1–42) and Phospholipid Bilayers to Accelerate the Aβ(1–42) Aggregation Below the Critical Micelle Concentration