Protein-protein association properties of human ßB2-crystallins.

ABSTRACT

Protein-protein association events are involved in many physiological and pathological processes. Cataract disease is a pathology that manifests protein aggregation of crystallins. ß-Crystallins are present in a high proportion in the eye lens. Therefore, the structural study of the dimerization properties of crystallins can shed light on the first stages of protein aggregation. In the present work, we examine the protein-protein association profiles of the human ßB2-crystallin by employing extensive coarse-grained molecular dynamics (CG-MD) and the Markov state analysis. Interestingly, our results clearly show important changes in the protein dimerization kinetics between wt-HßB2C and the deamidated systems. The two systems show dimeric conformations. However, the association and dissociation rates are very different. Our results show that the deamidated system can associate faster and dissociate slower than the wt- HßB2C. The deamidated system is in a slightly opened conformation with the Greek-key motifs well folded, suggesting that a complete unfolding of the protein is not required for aggregation. Our results describe the first stages of crystallin aggregation due to post-translational modifications.