Modification of Amyloid-β1-42 Fibril Structure by Methionine-35 Oxidation

2013 ◽  
Vol 37 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Liming Hou ◽  
Hyoung-gon Lee ◽  
Fang Han ◽  
Johnathan M. Tedesco ◽  
George Perry ◽  
...  
Keyword(s):  
Fibril Structure ◽  
Methionine 35

scholarly journals Anti-Parallel β-Hairpin Structure in Soluble Aβ Oligomers of Aβ40-Dutch and Aβ40-Iowa

2021 ◽  
Vol 22 (3) ◽  
pp. 1225
Author(s):  
Ziao Fu ◽  
William E. Van Nostrand ◽  
Steven O. Smith
Keyword(s):  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Aβ Oligomers ◽  
Dominant Component ◽  
Fibril Structure ◽  
Predominant Component ◽  
Aβ Aggregation ◽  
Aβ Fibrils ◽  
Soluble Aβ Oligomers ◽  
Β Sheet

The amyloid-β (Aβ) peptides are associated with two prominent diseases in the brain, Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). Aβ42 is the dominant component of cored parenchymal plaques associated with AD, while Aβ40 is the predominant component of vascular amyloid associated with CAA. There are familial CAA mutations at positions Glu22 and Asp23 that lead to aggressive Aβ aggregation, drive vascular amyloid deposition and result in degradation of vascular membranes. In this study, we compared the transition of the monomeric Aβ40-WT peptide into soluble oligomers and fibrils with the corresponding transitions of the Aβ40-Dutch (E22Q), Aβ40-Iowa (D23N) and Aβ40-Dutch, Iowa (E22Q, D23N) mutants. FTIR measurements show that in a fashion similar to Aβ40-WT, the familial CAA mutants form transient intermediates with anti-parallel β-structure. This structure appears before the formation of cross-β-sheet fibrils as determined by thioflavin T fluorescence and circular dichroism spectroscopy and occurs when AFM images reveal the presence of soluble oligomers and protofibrils. Although the anti-parallel β-hairpin is a common intermediate on the pathway to Aβ fibrils for the four peptides studied, the rate of conversion to cross-β-sheet fibril structure differs for each.

The fibril structure of type V collagen triple-helical domain

Micron ◽  
2001 ◽  
Vol 32 (3) ◽  
pp. 317-323 ◽  
Author(s):  
K Mizuno ◽  
E Adachi ◽  
Y Imamura ◽  
O Katsumata ◽  
T Hayashi
Keyword(s):  
Type V Collagen ◽  
Helical Domain ◽  
Fibril Structure ◽  
Triple Helical Domain ◽  
Type V

scholarly journals In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

The effect of exposing a critical hydrophobic patch on amyloidogenicity and fibril structure of insulin

2013 ◽  
Vol 440 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Yang Li ◽  
Lianqi Huang ◽  
Xin Yang ◽  
Chen Wang ◽  
Yue Sun ◽  
...  
Keyword(s):  
Hydrophobic Patch ◽  
Fibril Structure

Fibril Structure and Fibrillogenesis

Amyloidosis ◽  
2010 ◽  
pp. 1-14 ◽  
Author(s):  
Douglas J. Martin ◽  
Edward G. Randles ◽  
Marina Ramirez-Alvarado
Keyword(s):  
Fibril Structure

scholarly journals The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure

2020 ◽  
Author(s):  
Yunpeng Sun ◽  
Kun Zhao ◽  
Wencheng Xia ◽  
Jinge Gu ◽  
Yeyang Ma ◽  
...  
Keyword(s):  
Phase Separation ◽  
Nuclear Localization ◽  
Amyloid Fibril ◽  
Low Complexity ◽  
Nuclear Localization Sequence ◽  
Amyloid Aggregation ◽  
Dynamic Phase ◽  
Fibril Structure ◽  
Cytoplasmic Transport ◽  
Localization Sequence

AbstractHuman heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-β2 (Kapβ2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapβ2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminate structural understandings on the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapβ2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis.

scholarly journals Cryo-EM demonstrates the in vitro proliferation of an ex vivo amyloid fibril morphology by seeding

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Thomas Heerde ◽  
Matthies Rennegarbe ◽  
Alexander Biedermann ◽  
Dilan Savran ◽  
Peter B. Pfeiffer ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Ex Vivo ◽  
Proteinase K ◽  
Seed Structure ◽  
In Vitro Proliferation ◽  
Amyloid A ◽  
Fibril Structure ◽  
Proteolytic Stability ◽  
Fibril Morphology

AbstractSeveral studies showed that seeding of solutions of monomeric fibril proteins with ex vivo amyloid fibrils accelerated the kinetics of fibril formation in vitro but did not necessarily replicate the seed structure. In this research we use cryo-electron microscopy and other methods to analyze the ability of serum amyloid A (SAA)1.1-derived amyloid fibrils, purified from systemic AA amyloidosis tissue, to seed solutions of recombinant SAA1.1 protein. We show that 98% of the seeded fibrils remodel the full fibril structure of the main ex vivo fibril morphology, which we used for seeding, while they are notably different from unseeded in vitro fibrils. The seeded fibrils show a similar proteinase K resistance as ex vivo fibrils and are substantially more stable to proteolytic digestion than unseeded in vitro fibrils. Our data support the view that the fibril morphology contributes to determining proteolytic stability and that pathogenic amyloid fibrils arise from proteolytic selection.

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