+
Open data
-
Basic information
Entry | Database: PDB / ID: 8jhc | ||||||
---|---|---|---|---|---|---|---|
Title | FZD3 in inactive state | ||||||
![]() |
| ||||||
![]() | MEMBRANE PROTEIN / FZD3 / complex. | ||||||
Function / homology | ![]() dopaminergic neuron axon guidance / serotonergic neuron axon guidance / cell proliferation in midbrain / negative regulation of mitotic cell cycle, embryonic / establishment of planar polarity / midbrain morphogenesis / Wnt receptor activity / non-canonical Wnt signaling pathway / motor neuron migration / sympathetic ganglion development ...dopaminergic neuron axon guidance / serotonergic neuron axon guidance / cell proliferation in midbrain / negative regulation of mitotic cell cycle, embryonic / establishment of planar polarity / midbrain morphogenesis / Wnt receptor activity / non-canonical Wnt signaling pathway / motor neuron migration / sympathetic ganglion development / filopodium tip / Wnt-protein binding / post-anal tail morphogenesis / commissural neuron axon guidance / negative regulation of execution phase of apoptosis / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signaling pathway, planar cell polarity pathway / inner ear morphogenesis / positive regulation of neuroblast proliferation / hair follicle development / lateral plasma membrane / canonical Wnt signaling pathway / response to electrical stimulus / presynaptic active zone membrane / PDZ domain binding / Asymmetric localization of PCP proteins / neural tube closure / electron transport chain / G protein-coupled receptor activity / neuron differentiation / Ca2+ pathway / periplasmic space / electron transfer activity / apical plasma membrane / iron ion binding / response to xenobiotic stimulus / axon / neuronal cell body / heme binding / dendrite / glutamatergic synapse / cell surface / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Xu, F. / Zhang, Z. | ||||||
Funding support | 1items
| ||||||
![]() | ![]() Title: A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways. Authors: Zhibin Zhang / Xi Lin / Ling Wei / Yiran Wu / Lu Xu / Lijie Wu / Xiaohu Wei / Suwen Zhao / Xiangjia Zhu / Fei Xu / ![]() Abstract: The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. ...The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 208.2 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 157.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 42.6 KB | Display | |
Data in CIF | ![]() | 62.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 36262MC ![]() 8j9nC ![]() 8j9oC ![]() 8jh7C ![]() 8jhbC ![]() 8jhiC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 74095.141 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: inactive FZD3 Source: (gene. exp.) ![]() ![]() ![]() Cell line (production host): Sf9 / Production host: ![]() ![]() |
---|---|
#2: Antibody | Mass: 25704.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Antibody | Mass: 14927.301 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() ![]() |
#4: Antibody | Mass: 23209.820 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: complex of FZD3 with anti-Bril Fab and anti-Fab Nanobody Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Source (natural) |
| ||||||||||||||||
Source (recombinant) |
| ||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: DIFFRACTION / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 20 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 221700 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|