A mechanistic model for amorphous protein aggregation of immunoglobulin-like domains.

ABSTRACT: Protein aggregation is associated with many debilitating diseases including Alzheimer's, Parkinson's, and light-chain amyloidosis (AL). Additionally, such aggregation is a major problem in an industrial setting where antibody therapeutics often require high local concentrations of protein domains to be stable for substantial periods of time. However, despite a plethora of research in this field, dating back over 50 years, there is still no consensus on the mechanistic basis for protein aggregation. Here we use experimental data to derive a mechanistic model that well describes the aggregation of Titin I27, an immunoglobulin-like domain. Importantly, we find that models that are suitable for nucleated fibril formation do not fit our aggregation data. Instead, we show that aggregation procee

SUBMITTER: Borgia MB 

PROVIDER: S-EPMC3759167 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature