The structural basis of DKK-mediated inhibition of Wnt/LRP signaling.

The structural basis of DKK-mediated inhibition of Wnt/LRP signaling.
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DOI:
10.1126/scisignal.2003028
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发表时间:
2012-05-15
期刊:
影响因子:
7.3
通讯作者:
Wu D
Wu D
中科院分区:
生物学1区
文献类型:
--
作者:
Bao J;Zheng JJ;Wu D

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低密度脂蛋白受体相关蛋白 5 和 6 (LRP5/6) 通过与与 Wnt 蛋白结合的辅助受体卷曲蛋白 (Frizzled) 形成复合物来介导经典的 Wnt-β-连环蛋白信号传导。 Dickkopf (DKK) 相关蛋白通过直接结合 LRP5/6 的胞外域来抑制 Wnt 信号通路。然而,DKK 介导的拮抗作用机制迄今尚未完全清楚。 LRP6 胞外域与 DKK1 复合物的晶体结构以及诱变研究为 DKK 介导的抑制和通过 LRP5/6 的 Wnt 信号转导的分子基础提供了重要的见解。
Low-density lipoprotein receptor–related proteins 5 and 6 (LRP5/6) mediate canonical Wnt–β-catenin signaling by forming a complex with the co-receptor Frizzled, which binds to Wnt proteins. Dickkopf (DKK)–related proteins inhibit the Wnt signaling pathway by directly binding to the ectodomains of LRP5/6. However, the mechanism for DKK-mediated antagonism has not been fully understood as of yet. Crystal structures of the LRP6 ectodomain in complex with DKK1, along with mutagenesis studies, provide considerable insights into the molecular basis for DKK-mediated inhibition and Wnt signaling through LRP5/6.
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