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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8tzo
TitleStructure of human Wnt7a bound to WLS and CALR
Components
  • Calreticulin
  • Protein Wnt-7a
  • Protein wntless homolog
KeywordsSIGNALING PROTEIN
Function / homology
Function and homology information


postsynapse assembly / positive regulation of excitatory synapse assembly / regulation of axon diameter / positive regulation of protein localization to presynapse / skeletal muscle satellite cell activation / Wnt protein secretion / Calnexin/calreticulin cycle / asymmetric protein localization involved in cell fate determination / excitatory synapse assembly / cerebellar granule cell differentiation ...postsynapse assembly / positive regulation of excitatory synapse assembly / regulation of axon diameter / positive regulation of protein localization to presynapse / skeletal muscle satellite cell activation / Wnt protein secretion / Calnexin/calreticulin cycle / asymmetric protein localization involved in cell fate determination / excitatory synapse assembly / cerebellar granule cell differentiation / cytolytic granule / lens fiber cell development / positive regulation of Wnt protein secretion / synaptic vesicle recycling / Assembly of Viral Components at the Budding Site / WNT ligand biogenesis and trafficking / oviduct development / positive regulation of dendritic cell chemotaxis / cortical granule / central nervous system vasculogenesis / negative regulation of trophoblast cell migration / ATF6 (ATF6-alpha) activates chaperone genes / cell proliferation in forebrain / negative regulation of retinoic acid receptor signaling pathway / complement component C1q complex binding / cellular response to electrical stimulus / endoplasmic reticulum quality control compartment / uterus morphogenesis / intracellular glucocorticoid receptor signaling pathway / sequestering of calcium ion / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / regulation of meiotic nuclear division / secondary palate development / embryonic axis specification / cementum mineralization / response to glycoside / somatic stem cell division / sarcoplasmic reticulum lumen / protein folding in endoplasmic reticulum / hormone binding / sex differentiation / presynapse assembly / hindbrain development / Wnt-protein binding / stem cell development / nuclear export signal receptor activity / negative regulation of intracellular steroid hormone receptor signaling pathway / positive regulation of epithelial cell proliferation involved in wound healing / establishment of blood-brain barrier / molecular sequestering activity / cardiac muscle cell differentiation / neurotransmitter secretion / exocrine pancreas development / dendritic spine morphogenesis / frizzled binding / dorsal/ventral pattern formation / embryonic forelimb morphogenesis / embryonic hindlimb morphogenesis / Class B/2 (Secretin family receptors) / positive regulation of synapse assembly / wound healing, spreading of epidermal cells / Wnt signaling pathway, planar cell polarity pathway / regulation of postsynapse organization / anterior/posterior axis specification / protein maturation by protein folding / Scavenging by Class F Receptors / Scavenging by Class A Receptors / cortical actin cytoskeleton organization / nuclear androgen receptor binding / regulation of synaptic vesicle exocytosis / midbrain development / embryonic digit morphogenesis / cartilage condensation / establishment of cell polarity / response to testosterone / cellular response to lithium ion / smooth endoplasmic reticulum / somatic stem cell population maintenance / positive regulation of excitatory postsynaptic potential / regulation of presynapse assembly / protein localization to nucleus / mesoderm formation / positive regulation of Wnt signaling pathway / negative regulation of neuron differentiation / canonical Wnt signaling pathway / endomembrane system / cell fate commitment / chondrocyte differentiation / positive regulation of cell cycle / positive regulation of phagocytosis / : / protein folding chaperone / positive regulation of substrate adhesion-dependent cell spreading / cellular response to transforming growth factor beta stimulus / endocytic vesicle lumen / positive regulation of protein metabolic process / protein export from nucleus / endoplasmic reticulum-Golgi intermediate compartment membrane / axonogenesis / extracellular matrix
Similarity search - Function
Wnt-7 protein / Protein wntless / : / Wnt-binding factor required for Wnt secretion / Wnt protein, conserved site / Wnt-1 family signature. / Wnt / Wnt, C-terminal domain / wnt family / found in Wnt-1 ...Wnt-7 protein / Protein wntless / : / Wnt-binding factor required for Wnt secretion / Wnt protein, conserved site / Wnt-1 family signature. / Wnt / Wnt, C-terminal domain / wnt family / found in Wnt-1 / Calreticulin / Calreticulin family repeated motif signature. / Calreticulin/calnexin / Calreticulin/calnexin, P domain superfamily / Calreticulin/calnexin, conserved site / Calreticulin family / Calreticulin family signature 1. / Calreticulin family signature 2. / Endoplasmic reticulum targeting sequence. / Concanavalin A-like lectin/glucanase domain superfamily
Similarity search - Domain/homology
PALMITOLEIC ACID / Chem-POV / Protein Wnt-7a / Calreticulin / Protein wntless homolog
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 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 1.1May 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Protein Wnt-7a
B: Protein wntless homolog
C: Calreticulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)151,8697
Polymers149,5793
Non-polymers2,2904
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Protein , 3 types, 3 molecules ABC

#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 Calreticulin /


Mass: 48198.379 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P27797

-
Sugars , 1 types, 1 molecules

#4: Polysaccharide alpha-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D- ...alpha-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 1235.105 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpa1-3DManpa1-2DManpa1-2DManpa1-3DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/4,7,6/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5][a2122h-1a_1-5]/1-1-2-3-3-3-4/a4-b1_b4-c1_c3-d1_d2-e1_e2-f1_f3-g1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{[(3+1)][a-D-Manp]{[(2+1)][a-D-Manp]{[(2+1)][a-D-Manp]{[(3+1)][a-D-Glcp]{}}}}}}}LINUCSPDB-CARE

-
Non-polymers , 3 types, 3 molecules

#5: Chemical ChemComp-PAM / PALMITOLEIC ACID / Palmitoleic acid


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


Mass: 760.076 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C42H82NO8P / Feature type: SUBJECT OF INVESTIGATION / Comment: phospholipid*YM
#7: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Wnt7a-WLS-CALR Complex / Type: COMPLEX / Entity ID: #1-#3 / Source: MULTIPLE SOURCES
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 FIELDBright-field microscopy / 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

CTF correctionType: NONE
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 276377 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0038959
ELECTRON MICROSCOPYf_angle_d0.52712095
ELECTRON MICROSCOPYf_dihedral_angle_d8.7361245
ELECTRON MICROSCOPYf_chiral_restr0.0411300
ELECTRON MICROSCOPYf_plane_restr0.0051525

+
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