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- EMDB-73803: Cryo-EM structure of human Wntless in complex with Wnt5a at 1:1 s... -

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Basic information

Entry
Database: EMDB / ID: EMD-73803
TitleCryo-EM structure of human Wntless in complex with Wnt5a at 1:1 stoichiometry
Map datastructure of human Wntless in complex with Wnt5a at 1:1 stoichiometry
Sample
  • Complex: human Wntless in complex with Wnt5a at 1:1 stoichiometry
    • Protein or peptide: Protein Wnt-5a
    • Protein or peptide: Protein wntless homolog
  • Ligand: PALMITOLEIC ACID
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
  • Ligand: CHOLESTEROL
  • Ligand: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE
KeywordsWnt transporter / Wnt5a / Wnt signaling / MEMBRANE PROTEIN
Function / homology
Function and homology information


optic cup formation involved in camera-type eye development / receptor tyrosine kinase-like orphan receptor binding / chemoattraction of serotonergic neuron axon / hypophysis morphogenesis / positive regulation of timing of anagen / cervix development / positive regulation of protein kinase C activity / negative regulation of cell proliferation in midbrain / primary heart field specification / chemorepulsion of dopaminergic neuron axon ...optic cup formation involved in camera-type eye development / receptor tyrosine kinase-like orphan receptor binding / chemoattraction of serotonergic neuron axon / hypophysis morphogenesis / positive regulation of timing of anagen / cervix development / positive regulation of protein kinase C activity / negative regulation of cell proliferation in midbrain / primary heart field specification / chemorepulsion of dopaminergic neuron axon / mesodermal to mesenchymal transition involved in gastrulation / negative regulation of prostatic bud formation / postsynapse assembly / olfactory bulb interneuron development / chemoattractant activity involved in axon guidance / melanocyte proliferation / convergent extension involved in organogenesis / mesenchymal-epithelial cell signaling / negative regulation of melanin biosynthetic process / notochord morphogenesis / paraxial mesoderm formation / meiotic nuclear division / Wnt signaling pathway, calcium modulating pathway / regulation of postsynaptic cytosolic calcium ion concentration / convergent extension involved in axis elongation / urinary bladder development / Wnt protein secretion / positive regulation of hematopoietic stem cell proliferation / negative regulation of synapse assembly / negative regulation of mesenchymal cell proliferation / hindgut morphogenesis / macrophage derived foam cell differentiation / epithelial cell migration / regulation of branching involved in mammary gland duct morphogenesis / positive regulation of Wnt protein secretion / positive regulation of non-canonical Wnt signaling pathway / secondary heart field specification / negative regulation of axon extension involved in axon guidance / Negative regulation of TCF-dependent signaling by WNT ligand antagonists / primitive streak formation / WNT ligand biogenesis and trafficking / positive regulation of cell-cell adhesion mediated by cadherin / negative regulation of fibroblast growth factor receptor signaling pathway / WNT5A-dependent internalization of FZD2, FZD5 and ROR2 / excitatory synapse assembly / positive regulation of cartilage development / anterior/posterior axis specification, embryo / axon extension involved in axon guidance / establishment of planar polarity / midgut development / WNT5A-dependent internalization of FZD4 / lateral sprouting involved in mammary gland duct morphogenesis / cementum mineralization / secondary palate development / positive regulation of neuron projection arborization / presynapse assembly / positive regulation of meiotic nuclear division / positive regulation of T cell chemotaxis / embryonic skeletal system development / pericardium morphogenesis / mammary gland branching involved in thelarche / genitalia development / type B pancreatic cell development / mesenchymal cell proliferation / hindbrain development / non-canonical Wnt signaling pathway / cochlea morphogenesis / Wnt-protein binding / positive regulation of cytokine production involved in immune response / atrial septum development / WNT5:FZD7-mediated leishmania damping / post-anal tail morphogenesis / positive regulation of response to cytokine stimulus / establishment of epithelial cell apical/basal polarity / midbrain dopaminergic neuron differentiation / positive regulation of macrophage activation / exocrine pancreas development / frizzled binding / positive regulation of ossification / positive regulation of type I interferon-mediated signaling pathway / PCP/CE pathway / Class B/2 (Secretin family receptors) / positive regulation of thymocyte apoptotic process / cartilage development / inhibitory synapse assembly / lens development in camera-type eye / regulation of canonical NF-kappaB signal transduction / regulation of postsynapse organization / anterior/posterior axis specification / Wnt signaling pathway, planar cell polarity pathway / positive regulation of mesenchymal cell proliferation / positive regulation of macrophage cytokine production / embryonic digit morphogenesis / ventricular septum development / thymocyte apoptotic process / epithelial cell proliferation involved in mammary gland duct elongation / positive regulation of protein localization to synapse / negative regulation of fat cell differentiation / hematopoietic stem cell proliferation / heart looping
Similarity search - Function
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
Similarity search - Domain/homology
Protein Wnt-5a / Protein wntless homolog
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.64 Å
AuthorsGe Y / de Almeida Magalhaes T / Wu H / Wang Z / Salic A / Jiang J / Huang P
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM150878 United States
CitationJournal: To Be Published
Title: Conformational cycling of the Wntless transporter drives trafficking and secretion of Wnt morphogens
Authors: Ge Y / de Almeida Magalhaes T / Wu H / van den Boomen DJH / Nguyen TU / Dou T / Yadav GP / Lee S / Wang Z / Lemoff A / Luo X / Jin Z / Jiang J / Salic A / Huang P
History
DepositionNov 10, 2025-
Header (metadata) releaseJun 10, 2026-
Map releaseJun 10, 2026-
UpdateJun 10, 2026-
Current statusJun 10, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_73803.png

Downloads & links

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Map

FileDownload / File: emd_73803.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationstructure of human Wntless in complex with Wnt5a at 1:1 stoichiometry
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 320 pix.
= 265.6 Å		0.83 Å/pix.
x 320 pix.
= 265.6 Å		0.83 Å/pix.
x 320 pix.
= 265.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.164
Minimum - Maximum-1.3030255 - 1.8802546
Average (Standard dev.)0.0010689353 (±0.026431495)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 265.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_73803_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map A

Fileemd_73803_half_map_1.map
AnnotationHalf Map A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half Map B

Fileemd_73803_half_map_2.map
AnnotationHalf Map B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : human Wntless in complex with Wnt5a at 1:1 stoichiometry

EntireName: human Wntless in complex with Wnt5a at 1:1 stoichiometry
Components
  • Complex: human Wntless in complex with Wnt5a at 1:1 stoichiometry
    • Protein or peptide: Protein Wnt-5a
    • Protein or peptide: Protein wntless homolog
  • Ligand: PALMITOLEIC ACID
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
  • Ligand: CHOLESTEROL
  • Ligand: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE

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Supramolecule #1: human Wntless in complex with Wnt5a at 1:1 stoichiometry

SupramoleculeName: human Wntless in complex with Wnt5a at 1:1 stoichiometry
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Protein Wnt-5a

MacromoleculeName: Protein Wnt-5a / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 39.913203 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: FAQVVIEANS WWSLGMNNPV QMSEVYIIGA QPLCSQLAGL SQGQKKLCHL YQDHMQYIGE GAKTGIKECQ YQFRHRRWNC STVDNTSVF GRVMQIGSRE TAFTYAVSAA GVVNAMSRAC REGELSTCGC SRAARPKDLP RDWLWGGCGD NIDYGYRFAK E FVDARERE ...String:
FAQVVIEANS WWSLGMNNPV QMSEVYIIGA QPLCSQLAGL SQGQKKLCHL YQDHMQYIGE GAKTGIKECQ YQFRHRRWNC STVDNTSVF GRVMQIGSRE TAFTYAVSAA GVVNAMSRAC REGELSTCGC SRAARPKDLP RDWLWGGCGD NIDYGYRFAK E FVDARERE RIHAKGSYES ARILMNLHNN EAGRRTVYNL ADVACKCHGV SGSCSLKTCW LQLADFRKVG DALKEKYDSA AA MRLNSRG KLVQVNSRFN SPTTQDLVYI DPSPDYCVRN ESTGSLGTQG RLCNKTSEGM DGCELMCCGR GYDQFKTVQT ERC HCKFHW CCYVKCKKCT EIVDQFVCKA ADYKDDDDA

UniProtKB: Protein Wnt-5a

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Macromolecule #2: Protein wntless homolog

MacromoleculeName: Protein wntless homolog / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 66.088141 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAGAIIENMS TKKLCIVGGI LLVFQIIAFL VGGLIAPGPT TAVSYMSVKC VDARKNHHKT KWFVPWGPNH CDKIRDIEEA IPREIEAND IVFSVHIPLP HMEMSPWFQF MLFILQLDIA FKLNNQIREN AEVSMDVSLA YRDDAFAEWT EMAHERVPRK L KCTFTSPK ...String:
MAGAIIENMS TKKLCIVGGI LLVFQIIAFL VGGLIAPGPT TAVSYMSVKC VDARKNHHKT KWFVPWGPNH CDKIRDIEEA IPREIEAND IVFSVHIPLP HMEMSPWFQF MLFILQLDIA FKLNNQIREN AEVSMDVSLA YRDDAFAEWT EMAHERVPRK L KCTFTSPK TPEHEGRYYE CDVLPFMEIG SVAHKFYLLN IRLPVNEKKK INVGIGEIKD IRLVGIHQNG GFTKVWFAMK TF LTPSIFI IMVWYWRRIT MMSRPPVLLE KVIFALGISM TFINIPVEWF SIGFDWTWML LFGDIRQGIF YAMLLSFWII FCG EHMMDQ HERNHIAGYW KQVGPIAVGS FCLFIFDMCE RGVQLTNPFY SIWTTDIGTE LAMAFIIVAG ICLCLYFLFL CFMV FQVFR NISGKQSSLP AMSKVRRLHY EGLIFRFKFL MLITLACAAM TVIFFIVSQV TEGHWKWGGV TVQVNSAFFT GIYGM WNLY VFALMFLYAP SHKNYGEDQS NGDLGVHSGE ELQLTTTITH VDGPTEIYKL TRKEAQEAAA LEVLFQGPGA AEDQVD PRL IDGKHHHHHH HH

UniProtKB: Protein wntless homolog

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Macromolecule #4: PALMITOLEIC ACID

MacromoleculeName: PALMITOLEIC ACID / type: ligand / ID: 4 / Number of copies: 1 / Formula: PAM
Molecular weightTheoretical: 254.408 Da
Chemical component information

ChemComp-PAM:
PALMITOLEIC ACID

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Macromolecule #5: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 5 / Number of copies: 2 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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Macromolecule #6: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE

MacromoleculeName: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / type: ligand / ID: 6 / Number of copies: 5 / Formula: PCW
Molecular weightTheoretical: 787.121 Da
Chemical component information

ChemComp-PCW:
1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / DOPC, phospholipid*YM

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Macromolecule #7: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 7 / Number of copies: 1 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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Macromolecule #8: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE

MacromoleculeName: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE / type: ligand / ID: 8 / Number of copies: 1 / Formula: LPE
Molecular weightTheoretical: 510.708 Da
Chemical component information

ChemComp-LPE:
1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.64 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 104884
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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