We hypothesized that disruption of protein-carbohydrate interactions in the glycosylated domain of antibodies leads to the exposure of aggregation-prone motifs.
Thus, we hypothesized that disruption of sugar-protein, and more specifically CH-pi, interactions leads to exposure of aggregation-prone regions and to protein aggregation.
Our results support a mechanism for antibody aggregation via decreased protein-carbohydrate interactions, leading to the exposure of aggregation-prone regions, and to aggregation.
Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains.
This confirms that aggregation is induced by these parameters and further verifies that returning the aggregates to control solution following exposure to aggregation conditions is not sufficient to provoke significant reversal of the aggregation.
We assess the performance of commonly used models when confronted with such issues using simulation studies and compare their performance with a model specifically designed to acknowledge the effects of exposure aggregation.
At least a partial unfolding event must therefore take place in vivo to allow exposure of one or more aggregation-prone region(s) of the sequence to initiate amyloid formation.
The suggested approach is only applicable if there is some clustering of individual exposure concentrations within water districts or units of aggregation (ICC > > 0 and ICC < < 1).
The main reactions of proteins to UV-C radiation consist in the alteration of their secondary structures, exposure of hydrophobic residues, unfolding and aggregation.
However, conditions that promote protein unfolding may lead to exposure of such segments and facilitate aggregation.
The price for this flexibility, however, is the exposure of unfolded regions, prone to aggregation and irreversible damage.
