5GJE

Three-dimensional reconstruction of human LRP6 ectodomain complexed with Dkk1

Summary for 5GJE

• Entry DOI: 10.2210/pdb5gje/pdb
• EMDB information: 9501
• Descriptor: Low-density lipoprotein receptor-related protein 6, Dickkopf-related protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: wnt signaling, wnt co-receptor, lrp6, glycoprotein, antagonist, dkk1, conformational change, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 151666.37

Authors

Matoba, K.,Mihara, E.,Tamura-Kawakami, K.,Hirai, H.,Thompson, S.,Iwasaki, K.,Takagi, J. (deposition date: 2016-06-29, release date: 2017-01-18, Last modification date: 2024-10-23)

Primary citation

Matoba, K.,Mihara, E.,Tamura-Kawakami, K.,Miyazaki, N.,Maeda, S.,Hirai, H.,Thompson, S.,Iwasaki, K.,Takagi, J.
Conformational Freedom of the LRP6 Ectodomain Is Regulated by N-glycosylation and the Binding of the Wnt Antagonist Dkk1
Cell Rep, 18:32-40, 2017

PubMed Abstract: LDL-receptor-related protein 6 (LRP6) is a single-pass membrane glycoprotein with a large modular ectodomain and forms a higher order signaling platform upon binding Wnt ligands on the cell surface. Although multiple crystal structures are available for fragments of the LRP6 ectodomain, we lack a consensus view on the overall molecular architecture of the full-length LRP6 and its dynamic aspects. Here, we used negative-stain electron microscopy to probe conformational states of the entire ectodomain of LRP6 in solution and found that the four-module ectodomain undergoes a large bending motion hinged at the junction between the second and the third modules. Importantly, the extent of inter-domain motion is modulated by evolutionarily conserved N-glycan chains proximal to the joint. We also found that the LRP6 ectodomain becomes highly compact upon complexation with the Wnt antagonist Dkk1, suggesting a potential role for the ectodomain conformational change in the regulation of receptor oligomerization and signaling.

PubMed: 28052259
DOI: 10.1016/j.celrep.2016.12.017

Experimental method

ELECTRON MICROSCOPY (21 Å)