Protein-protein association properties of human βB2-crystallins.

Autor: Velasco-Bolom JL; Universidad Nacional Autonoma de Mexico, Facultad de Quimica, Ciudad de Mexico, Mexico., Domínguez L; Universidad Nacional Autonoma de Mexico, Facultad de Quimica, Ciudad de Mexico, Mexico.
Jazyk: angličtina
Zdroj: Proteins [Proteins] 2023 Jul 17. Date of Electronic Publication: 2023 Jul 17.
DOI: 10.1002/prot.26547
Abstrakt: Protein-protein association events are involved in many physiological and pathological processes. Cataract disease is a pathology that manifests protein aggregation of crystallins. β-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 βB2-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-HβB2C 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- HβB2C. 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.
(© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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