Buell, AK and Dhulesia, A and Mossuto, MF and Cremades, N and Kumita, JR and Dumoulin, M and Welland, ME and Knowles, TPJ and Salvatella, X and Dobson, CM (2011) Population of nonnative states of lysozyme variants drives amyloid fibril formation. J Am Chem Soc, 133. pp. 7737-7743.Full text not available from this repository.
The propensity of protein molecules to self-assemble into highly ordered, fibrillar aggregates lies at the heart of understanding many disorders ranging from Alzheimer's disease to systemic lysozyme amyloidosis. In this paper we use highly accurate kinetic measurements of amyloid fibril growth in combination with spectroscopic tools to quantify the effect of modifications in solution conditions and in the amino acid sequence of human lysozyme on its propensity to form amyloid fibrils under acidic conditions. We elucidate and quantify the correlation between the rate of amyloid growth and the population of nonnative states, and we show that changes in amyloidogenicity are almost entirely due to alterations in the stability of the native state, while other regions of the global free-energy surface remain largely unmodified. These results provide insight into the complex dynamics of a macromolecule on a multidimensional energy landscape and point the way for a better understanding of amyloid diseases.
|Uncontrolled Keywords:||Amyloid Humans Muramidase|
|Divisions:||Div B > Solid State Electronics and Nanoscale Science|
|Depositing User:||Unnamed user with email firstname.lastname@example.org|
|Date Deposited:||02 Sep 2016 16:23|
|Last Modified:||27 Sep 2016 22:55|