The investigation of Mesd and dkk1 binding sites on LRP6 domains: a new approach to anti-cancer protein design
- سال انتشار: 1394
- محل انتشار: یازدهمین کنگره بین المللی سرطان پستان
- کد COI اختصاصی: ICBCMED11_081
- زبان مقاله: انگلیسی
- تعداد مشاهده: 362
نویسندگان
PHD student of biophysics, Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Associate professor Biophysics, Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
چکیده
Signaling pathways are the most overriding part of 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.Interestingly, in triple negative breast cancer (TNBC), a highly aggressive subtype of breast carcinoma, Wnt/β catenin signaling is aberrantly activated because of overexpression of crucial co-receptor of the pathway LRP6 . The pathway is conserved and highly regulated with lots of mechanisms. DKK1, sFrp and Wif1 are the most structurally known inhibitor of the path. On the other hand, Mesd, an essential chaperon for proper folding of BP domains of LRP6, is a universal inhibitor and shows anti-cancer effect. Mesd and DKK1 bind to lrp6 and inhibit the pathway. But the mechanism of their inhibition is not fully understood. Here, we used a series blind and site-directed docking to create some of Mesd and DKK1 complexes with LRP6 to get a clearer picture about their interaction mode and binding sites on LRP6. The results show that some binding regions on LRP6 are overlapping and common for Mesd and DKK1. This finding is matched to some experimental assays. Interestingly affinity of Mesd to domain 12 of LRP6 is more than domain 34 and this is vice versa for DKK1. These results proposed new insight to design of novel anti-cancer proteinsor peptides based on Mesd and DKK1.کلیدواژه ها
breast cancer, anti cancer, docking simulationاطلاعات بیشتر در مورد COI
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