Exploring the aggregation propensity of γS-crystallin protein variants using two-dimensional spectroscopic tools.

The formation of amyloid fibrils is associated with many serious diseases as well as diverse biological functions. Despite the importance of these aggregates, predicting the aggregation propensity of a particular sequence is a major challenge. We report a joint 2D nuclear magnetic resonance (NMR) and ultraviolet (2DUV) study of fibrillization in the wild-type and two aggregation-prone mutants of the eye lens protein γS-crystallin.

Separating instability from aggregation propensity in γS-crystallin variants.

Molecular dynamics (MD) simulations, circular dichroism (CD), and dynamic light scattering (DLS) measurements were used to investigate the aggregation propensity of the eye-lens protein γS-crystallin. The wild-type protein was investigated along with the cataract-related G18V variant and the symmetry-related G106V variant. The MD simulations suggest that local sequence differences result in dramatic differences in dynamics and hydration between these two apparently similar point mutations.