8CTG

Extracellular architecture of an engineered canonical Wnt signaling ternary complex

Summary for 8CTG

• Entry DOI: 10.2210/pdb8ctg/pdb
• Related: 8FFE
• EMDB information: 26989
• Descriptor: Frizzled-8, Protein Wnt-8, Low-density lipoprotein receptor-related protein 6, ... (4 entities in total)
• Functional Keywords: signaling complex, beta-catenin, signaling protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 3
• Total formula weight: 125376.99

Authors

Tsutsumi, N.,Jude, K.M.,Garcia, K.C. (deposition date: 2022-05-14, release date: 2023-03-15, Last modification date: 2024-11-13)

Primary citation

Tsutsumi, N.,Hwang, S.,Waghray, D.,Hansen, S.,Jude, K.M.,Wang, N.,Miao, Y.,Glassman, C.R.,Caveney, N.A.,Janda, C.Y.,Hannoush, R.N.,Garcia, K.C.
Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for coreceptor discrimination.
Proc.Natl.Acad.Sci.USA, 120:e2218238120-e2218238120, 2023

PubMed Abstract: Wnt morphogens are critical for embryonic development and tissue regeneration. Canonical Wnts form ternary receptor complexes composed of tissue-specific Frizzled (Fzd) receptors together with the shared LRP5/6 coreceptors to initiate β-catenin signaling. The cryo-EM structure of a ternary initiation complex of an affinity-matured XWnt8-Frizzled8-LRP6 complex elucidates the basis of coreceptor discrimination by canonical Wnts by means of their N termini and linker domains that engage the LRP6 E1E2 domain funnels. Chimeric Wnts bearing modular linker "grafts" were able to transfer LRP6 domain specificity between different Wnts and enable non-canonical Wnt5a to signal through the canonical pathway. Synthetic peptides comprising the linker domain serve as Wnt-specific antagonists. The structure of the ternary complex provides a topological blueprint for the orientation and proximity of Frizzled and LRP6 within the Wnt cell surface signalosome.

PubMed: 36893265
DOI: 10.1073/pnas.2218238120

Experimental method

ELECTRON MICROSCOPY (3.8 Å)