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- EMDB-18890: Mouse teneurin-3 non-compact subunit - A1B1 isoform -

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Basic information

Entry
Database: EMDB / ID: EMD-18890
TitleMouse teneurin-3 non-compact subunit - A1B1 isoform
Map dataMap of mouse teneurin-3 A1B1 isoform non-compact subunit
Sample
  • Complex: mouse teneurin-3 A1B1 isoform ectodomain subunit
    • Protein or peptide: Teneurin-3
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
KeywordsSynaptic cell adhesion molecule / Homodimer / Cis-synaptic / CELL ADHESION
Function / homology
Function and homology information


regulation of homophilic cell adhesion / synaptic membrane adhesion / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / homophilic cell adhesion via plasma membrane adhesion molecules / neuron development / cell adhesion molecule binding / presynaptic active zone membrane / positive regulation of neuron projection development / neuron projection / protein heterodimerization activity ...regulation of homophilic cell adhesion / synaptic membrane adhesion / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / homophilic cell adhesion via plasma membrane adhesion molecules / neuron development / cell adhesion molecule binding / presynaptic active zone membrane / positive regulation of neuron projection development / neuron projection / protein heterodimerization activity / axon / glutamatergic synapse / signal transduction / protein homodimerization activity / identical protein binding / membrane / plasma membrane
Similarity search - Function
Teneurin intracellular, N-terminal / Teneurin Intracellular Region / Teneurin N-terminal domain profile. / Tox-GHH domain / GHH signature containing HNH/Endo VII superfamily nuclease toxin / : / YD repeat / Rhs repeat-associated core / Carboxypeptidase-like, regulatory domain superfamily / Six-bladed beta-propeller, TolB-like ...Teneurin intracellular, N-terminal / Teneurin Intracellular Region / Teneurin N-terminal domain profile. / Tox-GHH domain / GHH signature containing HNH/Endo VII superfamily nuclease toxin / : / YD repeat / Rhs repeat-associated core / Carboxypeptidase-like, regulatory domain superfamily / Six-bladed beta-propeller, TolB-like / Epidermal growth factor-like domain. / EGF-like domain profile. / EGF-like domain signature 2. / EGF-like domain signature 1. / EGF-like domain
Similarity search - Domain/homology
Biological speciesMus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsGogou C / Meijer DH
Funding support Netherlands, 1 items
OrganizationGrant numberCountry
Netherlands Organisation for Scientific Research (NWO)722.016.004 Netherlands
Citation
Journal: Nat Commun / Year: 2024
Title: Alternative splicing controls teneurin-3 compact dimer formation for neuronal recognition.
Authors: Christos Gogou / J Wouter Beugelink / Cátia P Frias / Leanid Kresik / Natalia Jaroszynska / Uwe Drescher / Bert J C Janssen / Robert Hindges / Dimphna H Meijer /
Abstract: Neuronal network formation is facilitated by recognition between synaptic cell adhesion molecules at the cell surface. Alternative splicing of cell adhesion molecules provides additional specificity ...Neuronal network formation is facilitated by recognition between synaptic cell adhesion molecules at the cell surface. Alternative splicing of cell adhesion molecules provides additional specificity in forming neuronal connections. For the teneurin family of cell adhesion molecules, alternative splicing of the EGF-repeats and NHL domain controls synaptic protein-protein interactions. Here we present cryo-EM structures of the compact dimeric ectodomain of two teneurin-3 isoforms that harbour the splice insert in the EGF-repeats. This dimer is stabilised by an EGF8-ABD contact between subunits. Cryo-EM reconstructions of all four splice variants, together with SAXS and negative stain EM, reveal compacted dimers for each, with variant-specific dimeric arrangements. This results in specific trans-cellular interactions, as tested in cell clustering and stripe assays. The compact conformations provide a structural basis for teneurin homo- and heterophilic interactions. Altogether, our findings demonstrate how alternative splicing results in rearrangements of the dimeric subunits, influencing neuronal recognition and likely circuit wiring.
#1: Journal: BioRxiv
Title: Mouse teneurin-3 non-compact subunit - A1B1 isoform
Authors: Gogou C / Meijer DH
History
DepositionNov 15, 2023-
Header (metadata) releaseMay 8, 2024-
Map releaseMay 8, 2024-
UpdateMay 8, 2024-
Current statusMay 8, 2024Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_18890.png

Downloads & links

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Map

FileDownload / File: emd_18890.map.gz / Format: CCP4 / Size: 67 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMap of mouse teneurin-3 A1B1 isoform non-compact subunit
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.84 Å/pix.
x 260 pix.
= 217.36 Å		0.84 Å/pix.
x 260 pix.
= 217.36 Å		0.84 Å/pix.
x 260 pix.
= 217.36 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.836 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0174
Minimum - Maximum-0.0974846 - 0.13649054
Average (Standard dev.)0.000111293826 (±0.0046009473)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions260260260
Spacing260260260
CellA=B=C: 217.36 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: Map of mouse teneurin-3 A1B1 isoform non-compact subunit...

Fileemd_18890_additional_1.map
AnnotationMap of mouse teneurin-3 A1B1 isoform non-compact subunit after focused classification and refinement on EGF8
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half map of mouse teneurin-3 A1B1 isoform non-compact subunit

Fileemd_18890_half_map_1.map
AnnotationHalf map of mouse teneurin-3 A1B1 isoform non-compact subunit
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Half map of mouse teneurin-3 A1B1 isoform non-compact subunit

Fileemd_18890_half_map_2.map
AnnotationHalf map of mouse teneurin-3 A1B1 isoform non-compact subunit
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : mouse teneurin-3 A1B1 isoform ectodomain subunit

EntireName: mouse teneurin-3 A1B1 isoform ectodomain subunit
Components
  • Complex: mouse teneurin-3 A1B1 isoform ectodomain subunit
    • Protein or peptide: Teneurin-3
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: mouse teneurin-3 A1B1 isoform ectodomain subunit

SupramoleculeName: mouse teneurin-3 A1B1 isoform ectodomain subunit / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 536.96 KDa

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Macromolecule #1: Teneurin-3

MacromoleculeName: Teneurin-3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 268.72225 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MARPLCTLLL LMATLAGALA GSHHHHHHGS QTENDTFENG KVNSDTVPTN TVSLPSGDNG KLGGFTHENN TIDSGELDIG RRAIQEVPP GIFWRSQLFI DQPQFLKFNI SLQKDALIGV YGRKGLPPSH TQYDFVELLD GSRLIAREQR NLVESERAGR Q ARSVSLHE ...String:
MARPLCTLLL LMATLAGALA GSHHHHHHGS QTENDTFENG KVNSDTVPTN TVSLPSGDNG KLGGFTHENN TIDSGELDIG RRAIQEVPP GIFWRSQLFI DQPQFLKFNI SLQKDALIGV YGRKGLPPSH TQYDFVELLD GSRLIAREQR NLVESERAGR Q ARSVSLHE AGFIQYLDSG IWHLAFYNDG KNPEQVSFNT IVIESVVECP RNCHGNGECV SGTCHCFPGF LGPDCSRAAC PV LCSGNGQ YSKGRCLCFS GWKGTECDVP TTQCIDPQCG GRGICIMGSC ACNSGYKGEN CEEADCLDPG CSNHGVCIHG ECH CNPGWG GSNCEILKTM CADQCSGHGT YLQESGSCTC DPNWTGPDCS NEICSVDCGS HGVCMGGSCR CEEGWTGPAC NQRA CHPRC AEHGTCKDGK CECSQGWNGE HCTIAHYLDK IVKEGCPGLC NSNGRCTLDQ NGWHCVCQPG WRGAGCDVAM ETLCT DSKD NEGDGLIDCM DPDCCLQSSC QNQPYCRGLP DPQDIISQSL QTPSQQAAKS FYDRISFLIG SDSTHVLPGE SPFNKS LAS VIRGQVLTAD GTPLIGVNVS FLHYSEYGYT ITRQDGMFDL VANGGASLTL VFERSPFLTQ YHTVWIPWNV FYVMDTL VM KKEENDIPSC DLSGFVRPSP IIVSSPLSTF FRSSPEDSPI IPETQVLHEE TTIPGTDLKL SYLSSRAAGY KSVLKITM T QAVIPFNLMK VHLMVAVVGR LFQKWFPASP NLAYTFIWDK TDAYNQKVYG LSEAVVSVGY EYESCLDLTL WEKRTAVLQ GYELDASNMG GWTLDKHHVL DVQNGILYKG NGENQFISQQ PPVVSSIMGN GRRRSISCPS CNGQADGNKL LAPVALACGI DGSLYVGDF NYVRRIFPSG NVTSVLELRN KDFRHSSNPA HRYYLATDPV TGDLYVSDTN TRRIYRPKSL TGAKDLTKNA E VVAGTGEQ CLPFDEARCG DGGKAVEATL MSPKGMAIDK NGLIYFVDGT MIRKVDQNGI ISTLLGSNDL TSARPLTCDT SM HISQVRL EWPTDLAINP MDNSIYVLDN NVVLQITENR QVRIAAGRPM HCQVPGVEYP VGKHAVQTTL ESATAIAVSY SGV LYITET DEKKINRIRQ VTTDGEISLV AGIPSECDCK NDANCDCYQS GDGYAKDAKL NAPSSLAASP DGTLYIADLG NIRI RAVSK NKPLLNSMNF YEVASPTDQE LYIFDINGTH QYTVSLVTGD YLYNFSYSND NDVTAVTDSN GNTLRIRRDP NRMPV RVVS PDNQVIWLTI GTNGCLKSMT AQGLELVLFT YHGNSGLLAT KSDETGWTTF FDYDSEGRLT NVTFPTGVVT NLHGDM DKA ITVDIESSSR EEDVSITSNL SSIDSFYTMV QDQLRNSYQI GYDGSLRIFY ASGLDSHYQT EPHVLAGTAN PTVAKRN MT LPGENGQNLV EWRFRKEQAQ GKVNVFGRKL RVNGRNLLSV DFDRTTKTEK IYDDHRKFLL RIAYDTSGHP TLWLPSSK L MAVNVTYSST GQIASIQRGT TSEKVDYDSQ GRIVSRVFAD GKTWSYTYLE KSMVLLLHSQ RQYIFEYDMW DRLSAITMP SVARHTMQTI RSIGYYRNIY NPPESNASII TDYNEEGLLL QTAFLGTSRR VLFKYRRQTR LSEILYDSTR VSFTYDETAG VLKTVNLQS DGFICTIRYR QIGPLIDRQI FRFSEDGMVN ARFDYSYDNS FRVTSMQGVI NETPLPIDLY QFDDISGKVE Q FGKFGVIY YDINQIISTA VMTYTKHFDA HGRIKEIQYE IFRSLMYWIT IQYDNMGRVT KREIKIGPFA NTTKYAYEYD VD GQLQTVY LNEKIMWRYN YDLNGNLHLL NPSSSARLTP LRYDLRDRIT RLGDVQYRLD EDGFLRQRGT EIFEYSSKGL LTR VYSKGS GWTVIYRYDG LGRRVSSKTS LGQHLQFFYA DLTYPTRITH VYNHSSSEIT SLYYDLQGHL FAMEISSGDE FYIA SDNTG TPLAVFSSNG LMLKQIQYTA YGEIYFDSNV DFQLVIGFHG GLYDPLTKLI HFGERDYDIL AGRWTTPDIE IWKRI GKDP APFNLYMFRN NNPASKIHDV KDYITDVNSW LVTFGFHLHN AIPGFPVPKF DLTEPSYELV KSQQWEDVPP IFGVQQ QVA RQAKAFLSLG KMAEVQVSRR KAGAEQSWLW FATVKSLIGK GVMLAVSQGR VQTNVLNIAN EDCIKVAAVL NNAFYLE NL HFTIEGKDTH YFIKTTTPES DLGTLRLTSG RKALENGINV TVSQSTTVVN GRTRRFADVE MQFGALALHV RYGMTLDE E KARILEQARQ RALARAWARE QQRVRDGEEG ARLWTEGEKR QLLSAGKVQG YDGYYVLSVE QYPELADSAN NIQFLRQSE IGKRAAA

UniProtKB: Teneurin-3

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Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 5 / 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

Concentration0.5 mg/mL
BufferpH: 7.8 / Details: 20 mM HEPES, 150 mM NaCl, 2mM CaCl2
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 22 K

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 69290
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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