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Aggregation and fib...
Aggregation and fibril morphology of the Arctic mutation of Alzheimer's Aβ peptide by CD, TEM, STEM and in situ AFM
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- Norlin, Nils (författare)
- Luleå tekniska universitet,Materialvetenskap
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- Hellberg, Magnus (författare)
- Luleå tekniska universitet
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- Filippov, Andrei (författare)
- Luleå tekniska universitet,Industriell miljö- och processteknik,Department of Physics, Kazan State University, Kazan, Russia
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- Sousa, Alioscka A (författare)
- Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA,Laboratory of Bioengineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, USA
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- Gröbner, Gerhard (författare)
- Umeå universitet,Kemiska institutionen,Dept Biol Chem, SE-90187 Luleå, Sweden,Department of Biological Chemistry, Institute of Chemistry, Umeå University, Umeå, Sweden
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- Leapman, Richard D (författare)
- Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA,Laboratory of Bioengineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, USA
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- Almqvist, Nils (författare)
- Luleå tekniska universitet,Materialvetenskap
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- Antzutkin, Oleg (författare)
- Luleå tekniska universitet,Industriell miljö- och processteknik,Department of Physics, Warwick University, Coventry, United Kingdom
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(creator_code:org_t)
- San Diego, CA, USA : Academic Press, 2012
- 2012
- Engelska.
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Ingår i: Journal of Structural Biology. - San Diego, CA, USA : Academic Press. - 1047-8477 .- 1095-8657. ; 180:1, s. 174-189
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Morphology of aggregation intermediates, polymorphism of amyloid fibrils and aggregation kinetics of the "Arctic" mutant of the Alzheimer's amyloid β-peptide, Aβ((1-40))(E22G), in a physiologically relevant Tris buffer (pH 7.4) were thoroughly explored in comparison with the human wild type Alzheimer's amyloid peptide, wt-Aβ((1-40)), using both in situ atomic force and electron microscopy, circular dichroism and thioflavin T fluorescence assays. For arc-Aβ((1-40)) at the end of the 'lag'-period of fibrillization an abrupt appearance of ∼3nm size 'spherical aggregates' with a homogeneous morphology, was identified. Then, the aggregation proceeds with a rapid growth of amyloid fibrils with a variety of morphologies, while the spherical aggregates eventually disappeared during in situ measurements. Arc-Aβ((1-40)) was also shown to form fibrils at much lower concentrations than wt-Aβ((1-40)): ⩽2.5μM and 12.5μM, respectively. Moreover, at the same concentration, 50μM, the aggregation process proceeds more rapidly for arc-Aβ((1-40)): the first amyloid fibrils were observed after c.a. 72h from the onset of incubation as compared to approximately 7days for wt-Aβ((1-40)). Amyloid fibrils of arc-Aβ((1-40)) exhibit a large variety of polymorphs, at least five, both coiled and non-coiled distinct fibril structures were recognized by AFM, while at least four types of arc-Aβ((1-40)) fibrils were identified by TEM and STEM and their mass-per-length statistics were collected suggesting supramolecular structures with two, four and six β-sheet laminae. Our results suggest a pathway of fibrillogenesis for full-length Alzheimer's peptides with small and structurally ordered transient spherical aggregates as on-pathway immediate precursors of amyloid fibrils.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
- NATURVETENSKAP -- Fysik -- Annan fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences -- Other Physics Topics (hsv//eng)
- NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
Nyckelord
- Amyloid β-peptide
- Arctic mutation
- Spherical aggregates
- Polymorphism of amyloid fibrils
- AFM
- TEM
- STEM
- Mass-per-length measurements
- Real time growth
- CD
- ThT assay
- Experimentell fysik
- Chemistry of Interfaces
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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