Related Experiment Video
Updated: Jan 25, 2026
Crystallization and Structural Determination of an Enzyme:Substrate Complex by Serial Crystallography in a Versatile Microfluidic Chip
Published on: March 20, 2021
Crystal structure of a mammalian Wnt-frizzled complex
Hidenori Hirai1,2, Kyoko Matoba1, Emiko Mihara1
1Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.
Abstract:
Wnt signaling plays fundamental roles in organogenesis, tissue regeneration and cancer, but high-resolution structural information of mammalian Wnt proteins is lacking. We solved a 2.8-Å resolution crystal structure of human Wnt3 in complex with mouse Frizzled 8 Cys-rich domain (CRD). Wnt3 grabs the receptor in a manner very similar to that found in Xenopus Wnt8 complexed with the same receptor. Unlike Xenopus Wnt8-bound CRD, however, Wnt3-bound CRD formed a symmetrical dimer in the crystal by exchanging the tip of the unsaturated acyl chain attached to each Wnt3, confirming the ability of Wnt and Frizzled CRD to form a 2:2 complex. The hypervariable 'linker' region of Wnt3 formed a β-hairpin protrusion opposite from the Frizzled binding interface, consistent with its proposed role in the coreceptor recognition. Direct binding between this segment and the Wnt coreceptor LRP6 was confirmed, enabling us to build a structural model of the Wnt-Frizzled-LRP6 ternary complex.
Insights
Researchers determined the structure of human Wnt3 bound to a Frizzled 8 receptor. This reveals how Wnt proteins interact with receptors and coreceptors, crucial for understanding development and disease.
Area of Science:
- Structural biology
- Molecular and cell biology
Background:
- Wnt signaling is vital for development, regeneration, and cancer.
- High-resolution structures of mammalian Wnt proteins were previously unavailable.
Purpose of the Study:
- To determine the high-resolution structure of human Wnt3 in complex with the mouse Frizzled 8 Cys-rich domain (CRD).
- To elucidate the molecular interactions between Wnt proteins, Frizzled receptors, and LRP6 coreceptors.
Main Methods:
- X-ray crystallography at 2.8-Å resolution.
- Structural analysis of the Wnt3-Frizzled 8 CRD complex.
Main Results:
- The crystal structure of human Wnt3 complexed with mouse Frizzled 8 CRD was solved.
- A 2:2 complex formation between Wnt3 and Frizzled 8 CRD was confirmed, involving dimerization of the CRD via lipid chain exchange.
- The Wnt3 linker region directly binds to the LRP6 coreceptor, facilitating the formation of a ternary complex.
Conclusions:
- The study provides the first high-resolution structure of a mammalian Wnt-Frizzled complex.
- Structural insights explain Wnt-Frizzled-LRP6 interactions, crucial for Wnt pathway signaling.
- This work lays the foundation for understanding Wnt signaling in various biological processes and diseases.
More Related Videos
Related Concept Videos
02:58Crystal Field Theory - Octahedral Complexes
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
02:42Ionic Crystal Structures
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
02:46Crystal Field Theory - Tetrahedral and Square Planar Complexes
Crystal field theory (CFT) is applicable to molecules in geometries other than octahedral. In octahedral complexes, the lobes of the dx2−y2 and dz2 orbitals point directly at the ligands. For tetrahedral complexes, the d orbitals remain in place, but with only four ligands located between the axes. None of the orbitals points directly at the tetrahedral ligands. However, the dx2−y2 and dz2 orbitals (along the Cartesian axes) overlap with the ligands less than the dxy,...
01:32Assembly of Complex Microtubule Structures
02:54Canonical Wnt Signaling Pathway
01:41Non-Canonical Wnt Signaling Pathways