4A0P

Crystal structure of LRP6P3E3P4E4

4A0P の概要

• エントリーDOI: 10.2210/pdb4a0p/pdb
• 分子名称: LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 6, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: signaling, lrp6, wnt signalling, wnt3a, dkk1, mesd
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 72812.04

構造登録者

Chen, S.,Malinauskas, T.,Aricescu, A.R.,Siebold, C.,Jones, E.Y. (登録日: 2011-09-11, 公開日: 2011-10-26, 最終更新日: 2024-11-06)

主引用文献

Chen, S.,Bubeck, D.,Macdonald, B.T.,Liang, W.X.,Mao, J.H.,Malinauskas, T.,Llorca, O.,Aricescu, A.R.,Siebold, C.,He, X.,Jones, E.Y.
Structural and Functional Studies of Lrp6 Ectodomain Reveal a Platform for Wnt Signaling.
Dev.Cell, 21:848-, 2011

PubMed Abstract: LDL-receptor-related protein 6 (LRP6), alongside Frizzled receptors, transduces Wnt signaling across the plasma membrane. The LRP6 ectodomain comprises four tandem β-propeller-EGF-like domain (PE) pairs that harbor binding sites for Wnt morphogens and their antagonists including Dickkopf 1 (Dkk1). To understand how these multiple interactions are integrated, we combined crystallographic analysis of the third and fourth PE pairs with electron microscopy (EM) to determine the complete ectodomain structure. An extensive inter-pair interface, conserved for the first-to-second and third-to-fourth PE interactions, contributes to a compact platform-like architecture, which is disrupted by mutations implicated in developmental diseases. EM reconstruction of the LRP6 platform bound to chaperone Mesd exemplifies a binding mode spanning PE pairs. Cellular and binding assays identify overlapping Wnt3a- and Dkk1-binding surfaces on the third PE pair, consistent with steric competition, but also suggest a model in which the platform structure supports an interplay of ligands through multiple interaction sites.

PubMed: 22000855
DOI: 10.1016/J.DEVCEL.2011.09.007

実験手法

X-RAY DIFFRACTION (1.9 Å)