Limits...
Polymorphism of amyloid-like fibrils can be defined by the concentration of seeds.

Sneideris T, Milto K, Smirnovas V - PeerJ (2015)

Bottom Line: The strains are enciphered by different misfolded conformations.Strain-like phenomena have also been reported in a number of other amyloid-forming proteins.Our findings could explain conformational switching between amyloid strains observed in a wide variety of in vivo and in vitro experiments.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biothermodynamics and Drug Design, Vilnius University, Institute of Biotechnology , Vilnius , Lithuania.

ABSTRACT
Prions are infectious proteins where the same protein may express distinct strains. The strains are enciphered by different misfolded conformations. Strain-like phenomena have also been reported in a number of other amyloid-forming proteins. One of the features of amyloid strains is the ability to self-propagate, maintaining a constant set of physical properties despite being propagated under conditions different from those that allowed initial formation of the strain. Here we report a cross-seeding experiment using strains formed under different conditions. Using high concentrations of seeds results in rapid elongation and new fibrils preserve the properties of the seeding fibrils. At low seed concentrations, secondary nucleation plays the major role and new fibrils gain properties predicted by the environment rather than the structure of the seeds. Our findings could explain conformational switching between amyloid strains observed in a wide variety of in vivo and in vitro experiments.

No MeSH data available.


Related in: MedlinePlus

Effect of sonication on the kinetics of aggregation (A–B) and stability of formed fibrils (C–D).The same amount of seeds (5%) was used in all experiments. Five data repeats plotted in (A) and (B). Standard errors calculated from 6 measurements using Student’s t-distribution at P = 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4563235&req=5

fig-6: Effect of sonication on the kinetics of aggregation (A–B) and stability of formed fibrils (C–D).The same amount of seeds (5%) was used in all experiments. Five data repeats plotted in (A) and (B). Standard errors calculated from 6 measurements using Student’s t-distribution at P = 0.05.

Mentions: As seen in Figs. 6A and 6B, in case of shorter (or in the absence of) sonication, kinetic curves have sigmoidal shapes, similar as in case of lower amount of longer-sonicated seeds. Fibrils formed in the presence of 30 s sonicated seeds (Fig. 6C) are more stable (midpoint at ∼2.8 M GuSCN) compared to the fibrils formed in presence of unsonicated seeds (midpoint at ∼2.3 M GuSCN).


Polymorphism of amyloid-like fibrils can be defined by the concentration of seeds.

Sneideris T, Milto K, Smirnovas V - PeerJ (2015)

Effect of sonication on the kinetics of aggregation (A–B) and stability of formed fibrils (C–D).The same amount of seeds (5%) was used in all experiments. Five data repeats plotted in (A) and (B). Standard errors calculated from 6 measurements using Student’s t-distribution at P = 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563235&req=5

fig-6: Effect of sonication on the kinetics of aggregation (A–B) and stability of formed fibrils (C–D).The same amount of seeds (5%) was used in all experiments. Five data repeats plotted in (A) and (B). Standard errors calculated from 6 measurements using Student’s t-distribution at P = 0.05.
Mentions: As seen in Figs. 6A and 6B, in case of shorter (or in the absence of) sonication, kinetic curves have sigmoidal shapes, similar as in case of lower amount of longer-sonicated seeds. Fibrils formed in the presence of 30 s sonicated seeds (Fig. 6C) are more stable (midpoint at ∼2.8 M GuSCN) compared to the fibrils formed in presence of unsonicated seeds (midpoint at ∼2.3 M GuSCN).

Bottom Line: The strains are enciphered by different misfolded conformations.Strain-like phenomena have also been reported in a number of other amyloid-forming proteins.Our findings could explain conformational switching between amyloid strains observed in a wide variety of in vivo and in vitro experiments.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biothermodynamics and Drug Design, Vilnius University, Institute of Biotechnology , Vilnius , Lithuania.

ABSTRACT
Prions are infectious proteins where the same protein may express distinct strains. The strains are enciphered by different misfolded conformations. Strain-like phenomena have also been reported in a number of other amyloid-forming proteins. One of the features of amyloid strains is the ability to self-propagate, maintaining a constant set of physical properties despite being propagated under conditions different from those that allowed initial formation of the strain. Here we report a cross-seeding experiment using strains formed under different conditions. Using high concentrations of seeds results in rapid elongation and new fibrils preserve the properties of the seeding fibrils. At low seed concentrations, secondary nucleation plays the major role and new fibrils gain properties predicted by the environment rather than the structure of the seeds. Our findings could explain conformational switching between amyloid strains observed in a wide variety of in vivo and in vitro experiments.

No MeSH data available.


Related in: MedlinePlus