[English] 日本語
Yorodumi
- PDB-8tzp: Structure of human Wnt7a bound to WLS and RECK -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8tzp
TitleStructure of human Wnt7a bound to WLS and RECK
Components
  • Protein Wnt-7a
  • Protein wntless homolog
  • Reversion-inducing cysteine-rich protein with Kazal motifs
KeywordsSIGNALING PROTEIN
Function / homology
Function and homology information


regulation of establishment of blood-brain barrier / postsynapse assembly / : / positive regulation of excitatory synapse assembly / positive regulation of protein localization to presynapse / skeletal muscle satellite cell activation / Wnt protein secretion / asymmetric protein localization involved in cell fate determination / cerebellar granule cell differentiation / excitatory synapse assembly ...regulation of establishment of blood-brain barrier / postsynapse assembly / : / positive regulation of excitatory synapse assembly / positive regulation of protein localization to presynapse / skeletal muscle satellite cell activation / Wnt protein secretion / asymmetric protein localization involved in cell fate determination / cerebellar granule cell differentiation / excitatory synapse assembly / blood vessel maturation / regulation of axon diameter / positive regulation of Wnt protein secretion / lens fiber cell development / WNT ligand biogenesis and trafficking / oviduct development / synaptic vesicle recycling / central nervous system vasculogenesis / cell proliferation in forebrain / uterus morphogenesis / embryonic axis specification / metalloendopeptidase inhibitor activity / cementum mineralization / Post-translational modification: synthesis of GPI-anchored proteins / secondary palate development / somatic stem cell division / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / sex differentiation / presynapse assembly / hindbrain development / positive regulation of epithelial cell proliferation involved in wound healing / Wnt-protein binding / stem cell development / regulation of extracellular matrix organization / establishment of blood-brain barrier / neurotransmitter secretion / dendritic spine morphogenesis / exocrine pancreas development / frizzled binding / dorsal/ventral pattern formation / embryonic forelimb morphogenesis / Class B/2 (Secretin family receptors) / Wnt signalosome / positive regulation of synapse assembly / embryonic hindlimb morphogenesis / regulation of postsynapse organization / regulation of canonical Wnt signaling pathway / sprouting angiogenesis / anterior/posterior axis specification / wound healing, spreading of epidermal cells / Wnt signaling pathway, planar cell polarity pathway / endopeptidase inhibitor activity / cartilage condensation / embryonic digit morphogenesis / regulation of synaptic vesicle exocytosis / establishment of cell polarity / midbrain development / organelle membrane / positive regulation of protein metabolic process / mesoderm formation / somatic stem cell population maintenance / positive regulation of excitatory postsynaptic potential / regulation of presynapse assembly / positive regulation of Wnt signaling pathway / cell fate commitment / chondrocyte differentiation / regulation of angiogenesis / canonical Wnt signaling pathway / coreceptor activity / side of membrane / cellular response to transforming growth factor beta stimulus / extracellular matrix organization / positive regulation of endothelial cell migration / embryo implantation / extracellular matrix / endomembrane system / axonogenesis / negative regulation of cell migration / cytokine activity / intracellular protein transport / positive regulation of JNK cascade / trans-Golgi network / serine-type endopeptidase inhibitor activity / Schaffer collateral - CA1 synapse / negative regulation of neurogenesis / Golgi lumen / Wnt signaling pathway / response to estrogen / neuron differentiation / endocytic vesicle membrane / positive regulation of canonical Wnt signaling pathway / response to estradiol / presynapse / early endosome membrane / cytoplasmic vesicle / angiogenesis / positive regulation of canonical NF-kappaB signal transduction / early endosome / receptor ligand activity / endoplasmic reticulum lumen
Similarity search - Function
Reversion-inducing cysteine-rich protein with Kazal motifs / : / : / RECK-like, EGF-like 1 domain / Reversion-inducing cysteine-rich with Kazal motifs, N-terminal / Wnt-7 protein / Protein wntless / : / : / Wntless-like, transmembrane domain ...Reversion-inducing cysteine-rich protein with Kazal motifs / : / : / RECK-like, EGF-like 1 domain / Reversion-inducing cysteine-rich with Kazal motifs, N-terminal / Wnt-7 protein / Protein wntless / : / : / Wntless-like, transmembrane domain / Wntless, GOLD domain / Wnt protein, conserved site / Wnt-1 family signature. / Wnt / Wnt, C-terminal domain / wnt family / found in Wnt-1 / Kazal serine protease inhibitors family signature. / Kazal-type serine protease inhibitor domain / Kazal type serine protease inhibitors / Kazal domain superfamily / Kazal domain / Kazal domain profile.
Similarity search - Domain/homology
PALMITOLEIC ACID / Chem-POV / Protein Wnt-7a / Reversion-inducing cysteine-rich protein with Kazal motifs / Protein wntless homolog
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.23 Å
AuthorsQi, X. / Hu, Q. / Li, X.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM135343 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)HL160487 United States
Welch FoundationI-1957 United States
CitationJournal: Cell / Year: 2023
Title: Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling.
Authors: Xiaofeng Qi / Qinli Hu / Nadia Elghobashi-Meinhardt / Tao Long / Hongwen Chen / Xiaochun Li /
Abstract: Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility ...Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECK engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling.
History
DepositionAug 27, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 18, 2023Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Oct 18, 2023Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1May 8, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.journal_id_CSD ..._citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 6, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification
Revision 1.3May 21, 2025Group: Data collection / Category: em_admin / em_software / Item: _em_admin.last_update / _em_software.name
Revision 1.1May 21, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / Category: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Protein Wnt-7a
B: Protein wntless homolog
C: Reversion-inducing cysteine-rich protein with Kazal motifs
hetero molecules


Theoretical massNumber of molelcules
Total (without water)208,9695
Polymers207,9543
Non-polymers1,0142
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein Protein Wnt-7a


Mass: 39062.977 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WNT7A / Production host: Homo sapiens (human) / References: UniProt: O00755
#2: Protein Protein wntless homolog


Mass: 62317.973 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WLS / Production host: Homo sapiens (human) / References: UniProt: Q5T9L3
#3: Protein Reversion-inducing cysteine-rich protein with Kazal motifs


Mass: 106573.461 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RECK / Production host: Homo sapiens (human) / References: UniProt: O95980
#4: Chemical ChemComp-PAM / PALMITOLEIC ACID


Mass: 254.408 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H30O2 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-POV / (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / POPC


Mass: 760.076 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C42H82NO8P / Feature type: SUBJECT OF INVESTIGATION / Comment: phospholipid*YM
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Wnt7a-WLS-RECK Complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 87543 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0037104
ELECTRON MICROSCOPYf_angle_d0.5899595
ELECTRON MICROSCOPYf_dihedral_angle_d6.868963
ELECTRON MICROSCOPYf_chiral_restr0.0411031
ELECTRON MICROSCOPYf_plane_restr0.0061207

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more