Role of Dynein Light Chains Tctex1 and Tcte3 in Apoptosis through In-silico Approaches

Abstract

Cytoplasmic dynein is a main motor protein that is accountable for microtubule minusend-directed activities in the eukaryotic cells. It transports a large range of cargoes and exhibits frequent functions during spindle congregation and chromosome separation. Dynein light chains (Tctex1 and Tcte3) add diversity in dynein function by connecting specific cargoes to the dynein complex. Tctex1 and Tcte3 are germ cell specific proteins with higher expression levels in testis and play a vital role in male germ cell development. Dynein complex plays an important role in the regulation of apoptosis by carrying pro- and anti-apoptotic cargoes. In this study, we investigated the role of Tctex1 and Tcte3 in apoptosis by computational approaches. We modeled Tctex1, Tcte3 tertiary structures to explore their structural similarities with dynein light chain of 8 kDa (LC8) which is experimentally known dynein light chain having role in apoptosis. Multiple docking procedures were employed to validate homodimerization and binding groove for pro-apoptotic protein Bim. Molecular dynamics simulation analysis was performed to confirm the stability and residual flexibility of apo-Tctex1,Tcte3 and their complexes with Bim. The simulation analysis demonstrated an overall stable binding pattern. We propose that like LC8, Tctex1 and Tcte3 exhibit similar dimer topology and binding grooves for Bim. Due to structural similarity, common binding partners, identical binding pocket and functional relevance, Tctex1 and Tcte3 may have common roles in apoptotic pathway by interacting with Bim in a similar manner to that of LC8.