Impact of deamidation on the structure and function of anti-apoptotic Bcl-xL.

Bcl-xL is an anti-apoptotic mitochondrial trans-membrane protein, known to play a crucial role in the survival of tumor cells. The deamidation of Bcl-xL is a pivotal switch that regulates its biological function. The potential impact of deamidation on the structure and dynamics of Bcl-xL is directly linked to the intrinsically disordered region (IDR), which is the main site for post-translational modifications (PTMs). In this study, we explored deamidation-induced conformational changes in Bcl- xL to gain insight into its loss of function by performing microsecond-long molecular dynamics (MD) simulations. MD simulation outcomes showed that the IDR motion and interaction patterns have changed notably upon deamidation. Principal component analysis (PCA) demonstrates significant differences between wild type and deamidated Bcl-xL and suggests that deamidation affects the structure and dynamics of Bcl-xL. Differences in contact patterns and essential dynamics in the binding groove (BG) are clear indications of deamidation-induced allosteric affects.