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- EMDB-52563: Cryo-EM structure of human sortilin ectodomain in complex with a ... -

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Basic information

Entry
Database: EMDB / ID: EMD-52563
TitleCryo-EM structure of human sortilin ectodomain in complex with a thyroglobulin C-terminal peptide
Map data
Sample
  • Complex: Human Sortilin ectodomain in complex with a thyroglobulin C-terminal peptide
    • Protein or peptide: Sortilin
    • Protein or peptide: Thyroglobulin
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsTrafficking / Vacuolar Protein Sorting / VPS10 / Beta propeller / Neurotensin binding receptor 3 / thyroglobulin / MEMBRANE PROTEIN
Function / homology
Function and homology information


neurotensin receptor activity, non-G protein-coupled / iodide transport / hormone biosynthetic process / Golgi to lysosome transport / plasma membrane to endosome transport / myotube differentiation / nerve growth factor receptor activity / cerebellar climbing fiber to Purkinje cell synapse / maintenance of synapse structure / retromer complex binding ...neurotensin receptor activity, non-G protein-coupled / iodide transport / hormone biosynthetic process / Golgi to lysosome transport / plasma membrane to endosome transport / myotube differentiation / nerve growth factor receptor activity / cerebellar climbing fiber to Purkinje cell synapse / maintenance of synapse structure / retromer complex binding / Golgi to endosome transport / endosome transport via multivesicular body sorting pathway / vesicle organization / nerve growth factor binding / protein targeting to lysosome / trans-Golgi network transport vesicle / thyroid hormone generation / clathrin-coated vesicle / regulation of myelination / Golgi cisterna membrane / endosome to lysosome transport / Golgi Associated Vesicle Biogenesis / negative regulation of fat cell differentiation / neurotrophin TRK receptor signaling pathway / : / thyroid gland development / extrinsic apoptotic signaling pathway via death domain receptors / neuropeptide signaling pathway / clathrin-coated pit / ossification / hormone activity / response to insulin / endocytosis / regulation of gene expression / cytoplasmic vesicle / nuclear membrane / early endosome / lysosome / endosome membrane / G protein-coupled receptor signaling pathway / lysosomal membrane / endoplasmic reticulum membrane / perinuclear region of cytoplasm / enzyme binding / cell surface / Golgi apparatus / signal transduction / extracellular space / extracellular region / identical protein binding / membrane / plasma membrane / cytosol
Similarity search - Function
Thyroglobulin / : / VPS10 / Sortilin, C-terminal / Sortilin, N-terminal / : / Sortilin, neurotensin receptor 3, C-terminal / Sortilin, neurotensin receptor 3, / VPS10 / Thyroglobulin type-1 repeat signature. ...Thyroglobulin / : / VPS10 / Sortilin, C-terminal / Sortilin, N-terminal / : / Sortilin, neurotensin receptor 3, C-terminal / Sortilin, neurotensin receptor 3, / VPS10 / Thyroglobulin type-1 repeat signature. / Thyroglobulin type-1 / Thyroglobulin type-1 superfamily / Thyroglobulin type-1 repeat / Thyroglobulin type-1 domain profile. / Thyroglobulin type I repeats. / Tyrosine-protein kinase ephrin type A/B receptor-like / Tyrosine-protein kinase ephrin type A/B receptor-like / Putative ephrin-receptor like / Carboxylesterase type B, conserved site / Carboxylesterases type-B signature 2. / Carboxylesterase, type B / Carboxylesterase family / Alpha/Beta hydrolase fold / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
Thyroglobulin / Sortilin
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.36 Å
AuthorsBoniardi I / Coscia F
Funding supportEuropean Union, 1 items
OrganizationGrant numberCountry
European Research Council (ERC)101041298European Union
CitationJournal: To Be Published
Title: Cryo-EM structure of human sortilin ectodomain in complex with a thyroglobulin C-terminal peptide
Authors: Boniardi I / Coscia F
History
DepositionJan 15, 2025-
Header (metadata) releaseDec 17, 2025-
Map releaseDec 17, 2025-
UpdateDec 17, 2025-
Current statusDec 17, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_52563.png

Downloads & links

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Map

FileDownload / File: emd_52563.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.75 Å/pix.
x 360 pix.
= 269.28 Å		0.75 Å/pix.
x 360 pix.
= 269.28 Å		0.75 Å/pix.
x 360 pix.
= 269.28 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.748 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.00659
Minimum - Maximum-0.018272955 - 0.034194976
Average (Standard dev.)0.000024024313 (±0.0005563174)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 269.28 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_52563_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_52563_half_map_2.map
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 Sortilin ectodomain in complex with a thyroglobulin C-termi...

EntireName: Human Sortilin ectodomain in complex with a thyroglobulin C-terminal peptide
Components
  • Complex: Human Sortilin ectodomain in complex with a thyroglobulin C-terminal peptide
    • Protein or peptide: Sortilin
    • Protein or peptide: Thyroglobulin
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Human Sortilin ectodomain in complex with a thyroglobulin C-termi...

SupramoleculeName: Human Sortilin ectodomain in complex with a thyroglobulin C-terminal peptide
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Details: Sortilin ectodomain, mature form generated by furin proteolysis of its N-terminal propeptide in complex with a thyroglobulin C-terminal peptide
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Sortilin

MacromoleculeName: Sortilin / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 82.94057 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QDRLDAPPPP AAPLPRWSGP IGVSWGLRAA AAGGAFPRGG RWRRSAPGED EECGRVRDFV AKLANNTHQH VFDDLRGSVS LSWVGDSTG VILVLTTFHV PLVIMTFGQS KLYRSEDYGK NFKDITDLIN NTFIRTEFGM AIGPENSGKV VLTAEVSGGS R GGRIFRSS ...String:
QDRLDAPPPP AAPLPRWSGP IGVSWGLRAA AAGGAFPRGG RWRRSAPGED EECGRVRDFV AKLANNTHQH VFDDLRGSVS LSWVGDSTG VILVLTTFHV PLVIMTFGQS KLYRSEDYGK NFKDITDLIN NTFIRTEFGM AIGPENSGKV VLTAEVSGGS R GGRIFRSS DFAKNFVQTD LPFHPLTQMM YSPQNSDYLL ALSTENGLWV SKNFGGKWEE IHKAVCLAKW GSDNTIFFTT YA NGSCKAD LGALELWRTS DLGKSFKTIG VKIYSFGLGG RFLFASVMAD KDTTRRIHVS TDQGDTWSMA QLPSVGQEQF YSI LAANDD MVFMHVDEPG DTGFGTIFTS DDRGIVYSKS LDRHLYTTTG GETDFTNVTS LRGVYITSVL SEDNSIQTMI TFDQ GGRWT HLRKPENSEC DATAKNKNEC SLHIHASYSI SQKLNVPMAP LSEPNAVGIV IAHGSVGDAI SVMVPDVYIS DDGGY SWTK MLEGPHYYTI LDSGGIIVAI EHSSRPINVI KFSTDEGQCW QTYTFTRDPI YFTGLASEPG ARSMNISIWG FTESFL TSQ WVSYTIDFKD ILERNCEEKD YTIWLAHSTD PEDYEDGCIL GYKEQFLRLR KSSVCQNGRD YVVTKQPSIC LCSLEDF LC DFGYYRPEND SKCVEQPELK GHDLEFCLYG REEHLTTNGY RKIPGDKCQG GVNPVREVKD LKKKCTSNFL SPEKQNSK S NSENLYFQSA GHHHHHHHHH H

UniProtKB: Sortilin

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Macromolecule #2: Thyroglobulin

MacromoleculeName: Thyroglobulin / type: protein_or_peptide / ID: 2
Details: This synthetic peptide corresponds to a thyroglobulin C-terminal peptide (residues 2749 to 2768)
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 2.211451 KDa
SequenceString:
SGLREDLLSL QEPGSKTYSK

UniProtKB: Thyroglobulin

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Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 1 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

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

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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

Concentration3.5 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
20.0 mMHEPES4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
150.0 mMNaClsodium chloride
0.5 %OGOctyl-beta-Glucoside
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV
Details1 mM of peptide

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Electron microscopy

MicroscopeTFS KRIOS
Specialist opticsEnergy filter - Name: TFS Selectris X / Energy filter - Slit width: 20 eV
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Number real images: 14574 / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 3023129
CTF correctionSoftware - Name: cryoSPARC (ver. 4.6.1) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

4po7

Final reconstructionNumber classes used: 1 / Resolution.type: BY AUTHOR / Resolution: 3.36 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 47561
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.6.2)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 5.0)
Final 3D classificationNumber classes: 4 / Software - Name: RELION (ver. 5.0)
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

4po7


Chain - Chain ID: A / Chain - Source name: PDB / Chain - Initial model type: experimental model
SoftwareName: Coot (ver. 0.9.8.95)
Output model

PDB-9i0o:
Cryo-EM structure of human sortilin ectodomain in complex with a thyroglobulin C-terminal peptide

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