Structural insight, mutation and interactions in human Beta-catenin and SOX17 protein: A molecular-level outlook for organogenesis.

Abstract

Essential human proteins; SOX17-HMG domain and beta-catenin uphold a major responsibility for vertebrate gastrulation and embryonic development. Earlier experimental assays document their interaction and states that upon M76A and G103R mutation, their interaction varied. Till date, there was no computational analysis for either of proteins as well as their respective residues for the interaction. The present study extracted and analyzed the experimentally validated 3D models of SOX17-HMG domain and beta-catenin. After analysis of the evolutionarily conserved residues and the sequence-level alteration, the mutated SOX17-HMG protein was re-modeled, demonstrated and energy minimized. Molecular dynamics simulation was performed upon the docked complex of beta-catenin with wild-type and mutant-type protein, individually. Comparable analysis for interaction studies revealed reduction of predominant ionic interactions from 16 (wild-type) to 5 (mutant-type). Glu residues from wild-type protein played a pivotal role forming 50% of the ionic interactions alone. Fascinatingly, statistically significant deductions for several stability calculations deduced the mutant-type protein/complex to form unsteady interaction with beta-catenin. Again, helix-to-coil transition in mutant-type protein supported its weaker conformation. This probe depicts the paramount molecular-level detailed scrutiny for the essential human proteins and disclosure of the mutational analysis, which might tend to hinder the signal transduction. It instigates the future development for the pharmaceutical research.