Frequency factors in a landscape model of filamentous protein aggregation.
Using quantitative measurements of protein aggregation rates, we develop a kinetic picture of protein conversion from a soluble to a fibrillar state which shows that a single free energy barrier to aggregation controls the addition of protein molecules into amyloid fibrils, while the characteristic sublinear concentration dependence emerges as a natural consequence of finite diffusion times. These findings suggest that this reaction does not follow a simple chemical mechanism, but rather operates in a way analogous to the landscape models of protein folding defined by stochastic dynamics on a characteristic energy surface.
Buell
Alexander K
AK
Nanoscience Centre, University of Cambridge, J J Thomson Avenue, Cambridge CB3 0FF, United Kingdom.
Blundell
Jamie R
JR
Dobson
Christopher M
CM
Welland
Mark E
ME
Terentjev
Eugene M
EM
Knowles
Tuomas P J
TP
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012995:Solubility; D013269:Stochastic Processes; D013816:Thermodynamics
D000682:Amyloid