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A Population Shift ...
A Population Shift between Sparsely Populated Folding Intermediates Determines Amyloidogenicity
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Karamanos, T. K. (författare)
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Pashley, C. L. (författare)
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Kalverda, A. P. (författare)
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Thompson, G. S. (författare)
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- Mayzel, Maxim (författare)
- Gothenburg University,Göteborgs universitet,Svenskt NMR-centrum vid Göteborgs universitet,Swedish NMR Centre at Göteborg University
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- Orekhov, Vladislav, 1966 (författare)
- Gothenburg University,Göteborgs universitet,Svenskt NMR-centrum vid Göteborgs universitet,Swedish NMR Centre at Göteborg University
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Radford, S. E. (författare)
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(creator_code:org_t)
- 2016-05-06
- 2016
- Engelska.
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 138:19, s. 6271-6280
- Relaterad länk:
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https://pubs.acs.org...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The balance between protein folding and misfolding is a crucial determinant of amyloid assembly. Transient intermediates that are sparsely populated during protein folding have been identified as key players in amyloid aggregation. However, due to their ephemeral nature, structural characterization of these species remains challenging. Here, using the power of nonuniformly sampled NMR methods we investigate the folding pathway of amyloidogenic and nonamyloidogenic variants of beta(2)-microglobulin (beta(2)m) in atomic detail. Despite folding via common intermediate states, we show that the decreased population of the aggregation-prone I-Trans state and population of a less stable, more dynamic species ablate amyloid formation by increasing the energy barrier for amyloid assembly. The results show that subtle changes in conformational dynamics can have a dramatic effect in determining whether a protein is amyloidogenic, without perturbation of the mechanism of protein folding.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- beta(2)-microglobulin-related amyloid fibrils
- human lysozyme
- neutral
- ph
- in-vitro
- beta-2-microglobulin
- aggregation
- proteins
- nmr
- prediction
- state
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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