Investigation of Probable MESD Binding Sites on LRP6 Domains

Signaling pathways are the most overriding part of intra and inter cellular communications and life development is coupled to increment of these pathways. The significance of their role in embryonic events and adult tissues homeostasis is exhaustively obvious and in human diseases, particularly cancers, some of these pathways are aberrantly active. So understanding the basis of this bad regulation is important to drug design and development.Interestingly, in triple negative breast cancer (TNBC), a highly aggressive subtype of breast carcinoma, Wnt/β catenin signaling is aberrantly activated and the reason of this state is overexpression of crucial co-receptor of the pathway LRP6 . The co-receptor has four extra cellular β propeller (BP) domains which have binding regions for Wnt ligands. MESD, an essential chaperon for proper folding of BP domains of LRP6, is a universal inhibitor of the pathway and showed anti-cancer effects in vitro and in vivo. There are some experimental evidence about binding of this molecular chaperon to LRP6 but the exact MESD binding sites are unexplored. Here we performed a series molecular docking procedures between MESD protein and the different BP domains of LRP6 co-receptor to find the most probable interacting regions. Our results suggest that there is at least one probable binding site on each LRP domain. It seems that this binding feature can raise the anticancer activity of the MESD. Our finding can help us to design new anticancer protein with higher efficacy.

کلیدواژه ها:

Wnt signaling ، Triple Negative Breast Cancer ، LRP6 ، MESD ، Molecular docking ، Anti-cancer