scholarly journals Investigating the Effects of Molecular Crowding on the Kinetics of Protein Aggregation

2020 ◽  
Vol 124 (44) ◽  
pp. 9829-9839
Author(s):  
John S. Schreck ◽  
John Bridstrup ◽  
Jian-Min Yuan
Keyword(s):  
Protein Aggregation ◽  
Molecular Crowding ◽  
Kinetics Of

scholarly journals Investigating the effects of molecular crowding on the kinetics of protein aggregation

2020 ◽  
Author(s):  
John S. Schreck ◽  
John Bridstrup ◽  
Jian-Min Yuan
Keyword(s):  
Protein Aggregation ◽  
Kinetic Equations ◽  
Macromolecular Crowding ◽  
Molecular Crowding ◽  
Dynamic Effects ◽  
Reaction Step ◽  
Speed Up ◽  
Kinetics Of

The thermodynamics and kinetics of protein folding and protein aggregation in vivo are of great importance in numerous scientific areas including fundamental biophysics research, nanotechnology, and medicine. However, these processes remain poorly understood in both in vivo and in vitro systems. Here we extend an established model for protein aggregation that is based on the kinetic equations for the moments of the polymer size distribution by introducing macromolecular crowding particles into the model using scaled-particle and transition-state theories. The model predicts that the presence of crowders can either speed up, cause no change to, or slow down the progress of the aggregation compared to crowder-free solutions, in striking agreement with experimental results from nine different amyloid-forming proteins that utilized dextran as the crowder. These different dynamic effects of macromolecular crowding can be understood in terms of the change of excluded volume associated with each reaction step.

scholarly journals Inhibition of Protein Aggregation by Several Antioxidants

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Samra Hasanbašić ◽  
Alma Jahić ◽  
Selma Berbić ◽  
Magda Tušek Žnidarič ◽  
Eva Žerovnik
Keyword(s):  
Vitamin C ◽  
Protein Aggregation ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Amyloid Fibril Formation ◽  
Transmission Electron ◽  
Tht Fluorescence ◽  
Shared Property ◽  
High Concentrations ◽  
Kinetics Of

Amyloid fibril formation is a shared property of all proteins; therefore, model proteins can be used to study this process. We measured protein aggregation of the model amyloid-forming protein stefin B in the presence and absence of several antioxidants. Amyloid fibril formation by stefin B was routinely induced at pH 5 and 10% TFE, at room temperature. The effects of antioxidants NAC, vitamin C, vitamin E, and the three polyphenols resveratrol, quercetin, and curcumin on the kinetics of fibril formation were followed using ThT fluorescence. Concomitantly, the morphology and amount of the aggregates and fibrils were checked by transmission electron microscopy (TEM). The concentration of the antioxidants was varied, and it was observed that different modes of action apply at low or high concentrations relative to the binding constant. In order to obtain more insight into the possible mode of binding, docking of NAC, vitamin C, and all three polyphenols was done to the monomeric form of stefin B.

scholarly journals SOD1 aggregation in ALS mice shows simplistic test tube behavior

2015 ◽  
Vol 112 (32) ◽  
pp. 9878-9883 ◽  
Author(s):  
Lisa Lang ◽  
Per Zetterström ◽  
Thomas Brännström ◽  
Stefan L. Marklund ◽  
Jens Danielsson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Protein Aggregation ◽  
Test Tube ◽  
Superoxide Dismutase 1 ◽  
Live Tissue ◽  
Antibody Assays ◽  
Kinetics Of ◽  
Aggregation Phenomena

A longstanding challenge in studies of neurodegenerative disease has been that the pathologic protein aggregates in live tissue are not amenable to structural and kinetic analysis by conventional methods. The situation is put in focus by the current progress in demarcating protein aggregation in vitro, exposing new mechanistic details that are now calling for quantitative in vivo comparison. In this study, we bridge this gap by presenting a direct comparison of the aggregation kinetics of the ALS-associated protein superoxide dismutase 1 (SOD1) in vitro and in transgenic mice. The results based on tissue sampling by quantitative antibody assays show that the SOD1 fibrillation kinetics in vitro mirror with remarkable accuracy the spinal cord aggregate buildup and disease progression in transgenic mice. This similarity between in vitro and in vivo data suggests that, despite the complexity of live tissue, SOD1 aggregation follows robust and simplistic rules, providing new mechanistic insights into the ALS pathology and organism-level manifestation of protein aggregation phenomena in general.

Sign in / Sign up

Export Citation Format

Share Document