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Response to crowded...
Response to crowded conditions reveals compact nucleus for amyloid formation of folded protein
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- Werner, Tony, 1990 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Horvath, Istvan, 1979 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Wittung Stafshede, Pernilla, 1968 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2021-01-19
- 2021
- Engelska.
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Ingår i: QRB Discovery. - : Cambridge University Press (CUP). - 2633-2892. ; 2
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Abstract
Ämnesord
Stäng
- Although the consequences of the crowded cell environments may affect protein folding, function and misfolding reactions, these processes are often studied in dilute solutions in vitro. We here used biophysical experiments to investigate the amyloid fibril formation process of the fish protein apo-β-parvalbumin in solvent conditions that mimic steric and solvation aspects of the in vivo milieu. Apo-β-parvalbumin is a folded protein that readily adopts an amyloid state via a nucleation-elongation mechanism. Aggregation experiments in the presence of macromolecular crowding agents (probing excluded volume, entropic effects) as well as small molecule osmolytes (probing solvation, enthalpic effects) revealed that both types of agents accelerate overall amyloid formation, but the elongation step was faster with macromolecular crowding agents but slower in the presence of osmolytes. The observations can be explained by the steric effects of excluded volume favoring assembled states and that amyloid nucleation does not involve monomer unfolding. In contrast, the solvation effects due to osmolyte presence promote nucleation but not elongation. Therefore, the amyloid-competent nuclei must be compact with less osmolytes excluded from the surface than either the folded monomers or amyloid fibers. We conclude that, in contrast to other amyloidogenic folded proteins, amyloid formation of apo-β-parvalbumin is accelerated by crowded cell-like conditions due to a nucleation process that does not involve large-scale protein unfolding.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
Nyckelord
- macromolecular crowding
- Amyloid formation
- β-parvalbumin
- osmolyte
- protein aggregation
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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