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- PDB-6cmx: Human Teneurin 2 extra-cellular region -

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Basic information

Entry
Database: PDB / ID: 6cmx
TitleHuman Teneurin 2 extra-cellular region
ComponentsTeneurin-2Teneurin
KeywordsMEMBRANE PROTEIN / Teneurin / CNS
Function / homology
Function and homology information


retrograde trans-synaptic signaling by trans-synaptic protein complex / positive regulation of filopodium assembly / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / : / neuron development / cell adhesion molecule binding / filopodium / axon guidance / cell-cell adhesion / PML body ...retrograde trans-synaptic signaling by trans-synaptic protein complex / positive regulation of filopodium assembly / heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules / : / neuron development / cell adhesion molecule binding / filopodium / axon guidance / cell-cell adhesion / PML body / cell-cell junction / cell junction / growth cone / postsynaptic membrane / dendritic spine / neuron projection / protein heterodimerization activity / signaling receptor binding / dendrite / synapse / calcium ion binding / Golgi apparatus / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / signal transduction / protein homodimerization activity / nucleus / plasma membrane
Similarity search - Function
Teneurin-2 / 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 / Quinoprotein amine dehydrogenase, beta chain-like ...Teneurin-2 / 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 / Quinoprotein amine dehydrogenase, beta chain-like / Six-bladed beta-propeller, TolB-like / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / 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
6alpha-alpha-mannobiose / alpha-D-mannopyranose / Teneurin-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.1 Å
AuthorsShalev-Benami, M. / Li, J. / Sudhof, T. / Skiniotis, G. / Arac, D.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01-GM120322 United States
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)R01 DK090165 United States
CitationJournal: Cell / Year: 2018
Title: Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse.
Authors: Jingxian Li / Moran Shalev-Benami / Richard Sando / Xian Jiang / Amanuel Kibrom / Jie Wang / Katherine Leon / Christopher Katanski / Olha Nazarko / Yue C Lu / Thomas C Südhof / Georgios ...Authors: Jingxian Li / Moran Shalev-Benami / Richard Sando / Xian Jiang / Amanuel Kibrom / Jie Wang / Katherine Leon / Christopher Katanski / Olha Nazarko / Yue C Lu / Thomas C Südhof / Georgios Skiniotis / Demet Araç /
Abstract: Teneurins (TENs) are cell-surface adhesion proteins with critical roles in tissue development and axon guidance. Here, we report the 3.1-Å cryoelectron microscopy structure of the human TEN2 ...Teneurins (TENs) are cell-surface adhesion proteins with critical roles in tissue development and axon guidance. Here, we report the 3.1-Å cryoelectron microscopy structure of the human TEN2 extracellular region (ECR), revealing a striking similarity to bacterial Tc-toxins. The ECR includes a large β barrel that partially encapsulates a C-terminal domain, which emerges to the solvent through an opening in the mid-barrel region. An immunoglobulin (Ig)-like domain seals the bottom of the barrel while a β propeller is attached in a perpendicular orientation. We further show that an alternatively spliced region within the β propeller acts as a switch to regulate trans-cellular adhesion of TEN2 to latrophilin (LPHN), a transmembrane receptor known to mediate critical functions in the central nervous system. One splice variant activates trans-cellular signaling in a LPHN-dependent manner, whereas the other induces inhibitory postsynaptic differentiation. These results highlight the unusual structural organization of TENs giving rise to their multifarious functions.
History
DepositionMar 6, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 25, 2018Provider: repository / Type: Initial release
Revision 1.1Feb 20, 2019Group: Author supporting evidence / Data collection / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2Dec 18, 2019Group: Author supporting evidence / Other / Category: atom_sites / pdbx_audit_support
Item: _atom_sites.fract_transf_matrix[1][1] / _atom_sites.fract_transf_matrix[2][2] ..._atom_sites.fract_transf_matrix[1][1] / _atom_sites.fract_transf_matrix[2][2] / _atom_sites.fract_transf_matrix[3][3] / _pdbx_audit_support.funding_organization
Revision 2.0Jul 29, 2020Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / database_PDB_caveat / entity / entity_name_com / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_molecule_features / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / pdbx_unobs_or_zero_occ_atoms / pdbx_validate_chiral / pdbx_validate_close_contact / struct_asym / struct_conn / struct_site / struct_site_gen
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.name / _chem_comp.type / _database_PDB_caveat.text / _pdbx_entity_nonpoly.entity_id / _pdbx_entity_nonpoly.name / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_unobs_or_zero_occ_atoms.auth_asym_id / _pdbx_unobs_or_zero_occ_atoms.auth_comp_id / _pdbx_unobs_or_zero_occ_atoms.auth_seq_id / _pdbx_unobs_or_zero_occ_atoms.label_asym_id / _pdbx_unobs_or_zero_occ_atoms.label_comp_id / _pdbx_validate_chiral.auth_asym_id / _pdbx_validate_chiral.auth_seq_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation

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Structure visualization

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Assembly

Deposited unit
A: Teneurin-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)227,46615
Polymers224,0061
Non-polymers3,46014
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Teneurin-2 / Teneurin / Ten-2 / Protein Odd Oz/ten-m homolog 2 / Tenascin-M2 / Ten-m2 / Teneurin transmembrane protein 2


Mass: 224005.812 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TENM2, KIAA1127, ODZ2, TNM2 / Production host: Trichoplusia ni (cabbage looper) / Strain (production host): High-Five / References: UniProt: Q9NT68*PLUS
#2: Polysaccharide alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 586.542 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-4DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/2,3,2/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1a_1-5]/1-1-2/a4-b1_b4-c1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][a-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][a-D-Manp]{}}}}LINUCSPDB-CARE
#3: Polysaccharide alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose / 6alpha-alpha-mannobiose


Type: oligosaccharide, Oligosaccharide / Class: Metabolism / Mass: 342.297 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: oligosaccharide / References: 6alpha-alpha-mannobiose
DescriptorTypeProgram
DManpa1-6DManpa1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a1122h-1a_1-5]/1-1/a6-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-Manp]{[(6+1)][a-D-Manp]{}}LINUCSPDB-CARE
#4: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 9
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#5: Sugar ChemComp-MAN / alpha-D-mannopyranose / Mannose


Type: D-saccharide, alpha linking / Mass: 180.156 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Formula: C6H12O6
IdentifierTypeProgram
DManpaCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
a-D-mannopyranoseCOMMON NAMEGMML 1.0
a-D-ManpIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
ManSNFG CARBOHYDRATE SYMBOLGMML 1.0

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: Teneurin 2 extra-cellular region / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT
Molecular weightValue: 0.215 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Trichoplusia ni (cabbage looper)
Buffer solutionpH: 8
SpecimenConc.: 0.15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid type: Quantifoil R2/2
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298.15 K

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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: OTHER
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 44 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.12_2829: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 426107 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00910387
ELECTRON MICROSCOPYf_angle_d1.22714140
ELECTRON MICROSCOPYf_dihedral_angle_d14.8025937
ELECTRON MICROSCOPYf_chiral_restr0.1381623
ELECTRON MICROSCOPYf_plane_restr0.0121772

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