Abstract

1. A model for the effect of time-dependent macromolecular crowding upon the rate of protein fibrillation was developed and presented as a possible explanation for the similar age dependence of the appearance of diverse neurodegenerative diseases that are attributed to the aggregation or fibrillation of different proteins with very different intrinsic colloidal stabilities (A. Minton). 2. An equilibrium model for the combined effect of macromolecular crowding and surface adsorption upon protein fibrillation was developed. The model predicts a highly cooperative transition between a slightly self-associating tracer species in bulk solution and a highly self-associated adsorbed tracer. Model estimates of the tendency of linear oligomers of various sizes to adsorb in the presence of unreactive crowders occupying various fractions of total solution volume are compared with the results of Monte Carlo simulations (T. Hoppe, A. Minton)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADK024957-07
Application #
8939505
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Hoppe, Travis; Minton, Allen P (2015) An equilibrium model for the combined effect of macromolecular crowding and surface adsorption on the formation of linear protein fibrils. Biophys J 108:957-66
Beg, Ilyas; Minton, Allen P; Hassan, Imtaiyaz et al. (2015) Thermal Stabilization of Proteins by Mono- and Oligosaccharides: Measurement and Analysis in the Context of an Excluded Volume Model. Biochemistry 54:3594-603
Wu, Di; Minton, Allen P (2013) Compensating effects of urea and trimethylamine-N-oxide on the heteroassociation of ?-chymotrypsin and soybean trypsin inhibitor. J Phys Chem B 117:3554-9
Minton, Allen P (2013) Quantitative assessment of the relative contributions of steric repulsion and chemical interactions to macromolecular crowding. Biopolymers 99:239-44
Fernández, Cristina; Minton, Allen P (2011) Effect of nonadditive repulsive intermolecular interactions on the light scattering of concentrated protein-osmolyte mixtures. J Phys Chem B 115:1289-93
Nagarajan, Sureshbabu; Amir, Dan; Grupi, Asaf et al. (2011) Modulation of functionally significant conformational equilibria in adenylate kinase by high concentrations of trimethylamine oxide attributed to volume exclusion. Biophys J 100:2991-9
Fodeke, Adedayo A; Minton, Allen P (2010) Quantitative characterization of polymer-polymer, protein-protein, and polymer-protein interaction via tracer sedimentation equilibrium. J Phys Chem B 114:10876-80
Tsao, Douglas; Minton, Allen P; Dokholyan, Nikolay V (2010) A didactic model of macromolecular crowding effects on protein folding. PLoS One 5:e11936
Jiao, Ming; Li, Hong-Tao; Chen, Jie et al. (2010) Attractive protein-polymer interactions markedly alter the effect of macromolecular crowding on protein association equilibria. Biophys J 99:914-23
Zhou, Huan-Xiang; Rivas, German; Minton, Allen P (2008) Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences. Annu Rev Biophys 37:375-97