A Limelight on Human Gp130 and Its Deleterious Mutations: A Computational Sequence Level Approach for Hepatocellular Carcinomas

This present study centers hepatocellular adenomas (IHCAs) and its effect due to gp130 mutations based on evolutionary relationship as well as literature survey involving wet-laboratory experiments. Generally, IL6 family of cytokines interacts with their respective IL6 receptors and gp130, which in turn induces JAK/STAT pathway to activate pro-inflammatory STAT3 target genes. The activation of this signaling pathway poses a paramount impact in tumor development. Several mutations in gp130 were studied through evolutionary relatedness which aggravates the tumorigenesis. Mutations in IL6Rα binding domain region (positions: 131–218 of human gp130) from MSA were also studied. A point mutation: A200V in Otolemur garnettii showed the deleterious effect. Further, the deleterious effect upon proteins’ functionality was also examined and seven mutations were responsible for it. V189G showed the highest destabilizing effect. Unstable conformation shifts were also observed in the proteins due to their respective mutations. Change in the transmembrane region, change in gp130s’ ordered interface, loss of sulfation at Y186, lesser relative solvent accessibility, change in protein stability and metal binding properties were also observed in several mutations. These mutations might be responsible for changing the activity of the IL6Rα binding domain region of human gp130 protein triggering hepatocellular adenomas. Therefore, targeting gp130 and its mutations would serve as an important therapeutic target to cause apoptosis of the tumor cells. Interaction studies within the three proteins for the respective mutations could also to be in the future pathway of research. It would also aim to instigate the drug discovery for the same.