3SOQ

The structure of the first YWTD beta propeller domain of LRP6 in complex with a DKK1 peptide

3SOQ の概要

• エントリーDOI: 10.2210/pdb3soq/pdb
• 関連するPDBエントリー: 3SOB 3SOV
• 分子名称: Low-density lipoprotein receptor-related protein 6, Dickkopf-related protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: beta propeller, protein binding-antagonist complex, protein binding/antagonist
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36988.32

構造登録者

Wang, W.,Bourhis, E.,Zhang, Y.,Rouge, L.,Wu, Y.,Franke, Y.,Cochran, A.G. (登録日: 2011-06-30, 公開日: 2011-09-21, 最終更新日: 2024-11-27)

主引用文献

Bourhis, E.,Wang, W.,Tam, C.,Hwang, J.,Zhang, Y.,Spittler, D.,Huang, O.W.,Gong, Y.,Estevez, A.,Zilberleyb, I.,Rouge, L.,Chiu, C.,Wu, Y.,Costa, M.,Hannoush, R.N.,Franke, Y.,Cochran, A.G.
Wnt antagonists bind through a short peptide to the first beta-propeller domain of LRP5/6.
Structure, 19:1433-1442, 2011

PubMed Abstract: The Wnt pathway inhibitors DKK1 and sclerostin (SOST) are important therapeutic targets in diseases involving bone loss or damage. It has been appreciated that Wnt coreceptors LRP5/6 are also important, as human missense mutations that result in bone overgrowth (bone mineral density, or BMD, mutations) cluster to the E1 propeller domain of LRP5. Here, we report a crystal structure of LRP6 E1 bound to an antibody, revealing that the E1 domain is a peptide recognition module. Remarkably, the consensus E1 binding sequence is a close match to a conserved tripeptide motif present in all Wnt inhibitors that bind LRP5/6. We show that this motif is important for DKK1 and SOST binding to LRP6 and for inhibitory function, providing a detailed structural explanation for the effect of the BMD mutations.

PubMed: 21944579
DOI: 10.1016/j.str.2011.07.005

実験手法

X-RAY DIFFRACTION (1.9 Å)