Polymerization mechanism of polypeptide chain aggregation

Nonnative Aggregation of an IgG1 Antibody in Acidic Conditions, Part 2: Nucleation and Growth Kinetics with Competing Growth Mechanisms

“…Results section). The questions above notwithstanding, the results in Figure 4 are consistent with behavior seen previously for structurally dissimilar proteins such as aCgn 13 and P22 tailspike, 18 in which aggregate growth can involve a competition between monomer addition and condensation polymerization. Additionally, the results here are qualitatively consistent with more recent results for aCgn 12 and a series of IgG1 antibodies; 45 in that, the mechanism changes from the creation of soluble aggregates to insoluble aggregates with increase in pH under acidic conditions.…”

“…3,7 Aggregation pathways have a number of common features across a range of proteins. 2,5,[8][9][10][11][12][13][14][15][16][17][18] Aggregate formation often involves some or all of the following steps, depending on the protein and conditions of interest: monomer unfolding and/ or misfolding, 9,11,17 reversible self-association, 15,16,19 nucleation or creation of the smallest stable (i.e., net irreversible) aggregates, 8,10,13 subsequent growth of soluble aggregates by monomer addition and/ or aggregate-aggregate coalescence or condensation polymerization, [12][13][14]18 and aggregate precipitation and/or macroscopic particle formation. 12 A number of theoretical and experimental models capture some of these steps in the multistep process of aggregation.…”

Principles, approaches, and challenges for predicting protein aggregation rates and shelf life

“…The term polymerization is often used to indicate that large or high-MW soluble aggregates are ultimately produced. 35,37,[49][50][51] However, it can just as easily be applied to systems where growth is slow or similar in rate to nucleation. In such cases, this simply means the distribution of soluble aggregate sizes would include only small oligomers on the time scale of interest.…”

Frequencies of amino acid strings in globular protein sequences indicate suppression of blocks of consecutive hydrophobic residues

“…A common failure mode is the self-association of folding intermediates, leading to an aggregated biological state (Speed et al 1997;Wetzel 1997). In a number of well-studied systems this off-pathway reaction has been shown to be associated with partially folded intermediates.…”