Evaluation of Fam83h Interaction with Cytoskeleton Keratin- An In-Silico Study

Abstract

Background and Aim: Fam83h Protein is a non-secretory protein that interacts with Casein Kinase1Alpha1(CSNK1A1) through its N-terminal. Materials and Methods: In this study, the C-terminal domains of Fam83h in human and mouse were modeled using the I-TASER software for prediction of protein structure and function. The molecular dynamics (MD) simulations were performed by GROMACS version 5.0.2 to investigate their temporal behavior. FEL analysis was done for each model after MD. Protein-protein docking was done by PIPER to investigate the interaction of Fam83h C-terminal with cytoskeletal keratins5 as a cellular keratin model. Results: The results showed that the human protein is more stable and compact than the mouse protein. Assessment of the interaction between the C-terminal of the mouse Fam83h and Keratin-5 proteins showed the residues Arg378, Pro391, Ser663, Glu710, Arg923 in mouse Fam83h protein made hydrogen bonds with Leu474, Arg417, Tyr453, Glu 397, Gln 396 and Glu 390 of the chain A and B of mouse keratin-5, respectively. Human Fam83h and keratin 5 form hydrogen bonds via residues of Thr433, His447 and Arg477 and Leu473, Gly476, Glu420 and Arg407. Conclusion: According to the previous experimental reports, Fam83h can interact with keratin cytoskeleton and has a role in cancer progression. It can be concluded that Fam83h protein can directly interact with keratin filaments through its C-terminal. Therefore, our hypothesis based on in-silico study is: non-sense mutation in C-terminal of Fam83h protein may lead to truncated protein and subsequently disruption of keratin cytoskeleton bundling which can be regarded as a mechanism involved in cancer progression.

Keywords

• fam83h protein
• keratin-5
• csnk1a1
• molecular dynamics simulation