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- EMDB-50135: Cryo-EM structure of SV2B-Hc-A1 complex -

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Basic information

Entry
Database: EMDB / ID: EMD-50135
TitleCryo-EM structure of SV2B-Hc-A1 complex
Map data
Sample
  • Complex: Cryo-EM structure of SV2B-Hc-A1 complex
    • Protein or peptide: Synaptic vesicle glycoprotein 2B
    • Protein or peptide: Botulinum neurotoxin A heavy chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
Keywordstransporter / botulinum neurotoxin / synaptic vesicle glycoprotein / MEMBRANE PROTEIN
Function / homology
Function and homology information


Toxicity of botulinum toxin type F (botF) / Toxicity of botulinum toxin type D (botD) / Toxicity of botulinum toxin type E (botE) / Toxicity of botulinum toxin type A (botA) / ganglioside GT1b binding / regulation of presynaptic cytosolic calcium ion concentration / bontoxilysin / host cell presynaptic membrane / host cell cytoplasmic vesicle / host cell cytosol ...Toxicity of botulinum toxin type F (botF) / Toxicity of botulinum toxin type D (botD) / Toxicity of botulinum toxin type E (botE) / Toxicity of botulinum toxin type A (botA) / ganglioside GT1b binding / regulation of presynaptic cytosolic calcium ion concentration / bontoxilysin / host cell presynaptic membrane / host cell cytoplasmic vesicle / host cell cytosol / neurotransmitter transport / regulation of synaptic vesicle exocytosis / transmembrane transporter activity / protein transmembrane transporter activity / acrosomal vesicle / metalloendopeptidase activity / synaptic vesicle membrane / synaptic vesicle / toxin activity / chemical synaptic transmission / host cell plasma membrane / proteolysis / extracellular region / zinc ion binding / membrane / plasma membrane
Similarity search - Function
: / SV2A/B/C luminal domain / Synaptic vesicle protein SV2 / Sugar transporter, conserved site / Major facilitator, sugar transporter-like / Sugar (and other) transporter / Clostridium neurotoxin, translocation / Clostridium neurotoxin, Translocation domain / Clostridium neurotoxin, translocation domain / Clostridial neurotoxin zinc protease ...: / SV2A/B/C luminal domain / Synaptic vesicle protein SV2 / Sugar transporter, conserved site / Major facilitator, sugar transporter-like / Sugar (and other) transporter / Clostridium neurotoxin, translocation / Clostridium neurotoxin, Translocation domain / Clostridium neurotoxin, translocation domain / Clostridial neurotoxin zinc protease / Botulinum/Tetanus toxin, catalytic chain / Clostridium neurotoxin, receptor-binding C-terminal / Clostridium neurotoxin, receptor binding N-terminal / Clostridium neurotoxin, C-terminal receptor binding / Clostridium neurotoxin, N-terminal receptor binding / Kunitz inhibitor STI-like superfamily / Major facilitator superfamily / Major Facilitator Superfamily / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily / Neutral zinc metallopeptidases, zinc-binding region signature. / Concanavalin A-like lectin/glucanase domain superfamily
Similarity search - Domain/homology
Botulinum neurotoxin type A / Synaptic vesicle glycoprotein 2B
Similarity search - Component
Biological speciesClostridium botulinum (bacteria) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.67 Å
AuthorsKhanppnavar B / Leka O / Korkhov V / Kammerer R
Funding support Switzerland, 2 items
OrganizationGrant numberCountry
Swiss National Science Foundation310030_212253 Switzerland
Swiss National Science Foundation198545 Switzerland
CitationJournal: Nat Commun / Year: 2025
Title: Cryo-EM structure of the botulinum neurotoxin A/SV2B complex and its implications for translocation.
Authors: Basavraj Khanppnavar / Oneda Leka / Sushant K Pal / Volodymyr M Korkhov / Richard A Kammerer /
Abstract: Botulinum neurotoxin A1 (BoNT/A1) belongs to the most potent toxins and is used as a major therapeutic agent. Neurotoxin conformation is crucial for its translocation to the neuronal cytosol, a key ...Botulinum neurotoxin A1 (BoNT/A1) belongs to the most potent toxins and is used as a major therapeutic agent. Neurotoxin conformation is crucial for its translocation to the neuronal cytosol, a key process for intoxication that is only poorly understood. To gain molecular insights into the steps preceding toxin translocation, we determine cryo-EM structures of BoNT/A1 alone and in complex with its receptor synaptic vesicle glycoprotein 2B (SV2B). In solution, BoNT/A1 adopts a unique, semi-closed conformation. The toxin changes its structure into an open state upon receptor binding with the translocation domain (H) and the catalytic domain (LC) remote from the membrane, suggesting translocation incompatibility. Under acidic pH conditions, where translocation is initiated, receptor-bound BoNT/A1 switches back into a semi-closed conformation. This conformation brings the LC and H close to the membrane, suggesting that a translocation-competent state of the toxin is required for successful LC transport into the neuronal cytosol.
History
DepositionApr 20, 2024-
Header (metadata) releaseMar 12, 2025-
Map releaseMar 12, 2025-
UpdateMar 12, 2025-
Current statusMar 12, 2025Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_50135.png

Downloads & links

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Map

FileDownload / File: emd_50135.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.65 Å/pix.
x 440 pix.
= 286. Å		0.65 Å/pix.
x 440 pix.
= 286. Å		0.65 Å/pix.
x 440 pix.
= 286. Å

Surface

Projections

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Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.65 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-1.6164607 - 2.2778187
Average (Standard dev.)0.000693174 (±0.035160687)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 286.0 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_50135_msk_1.map
Projections & Slices
AxesZYX

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Histogram

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Half map: #2

Fileemd_50135_half_map_1.map
Projections & Slices
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Half map: #1

Fileemd_50135_half_map_2.map
Projections & Slices
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Sample components

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Entire : Cryo-EM structure of SV2B-Hc-A1 complex

EntireName: Cryo-EM structure of SV2B-Hc-A1 complex
Components
  • Complex: Cryo-EM structure of SV2B-Hc-A1 complex
    • Protein or peptide: Synaptic vesicle glycoprotein 2B
    • Protein or peptide: Botulinum neurotoxin A heavy chain
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose

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Supramolecule #1: Cryo-EM structure of SV2B-Hc-A1 complex

SupramoleculeName: Cryo-EM structure of SV2B-Hc-A1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Details: Cryo-EM structure of human SV2B bound to the Hc domain of BoNT-A1
Source (natural)Organism: Clostridium botulinum (bacteria)
Molecular weightTheoretical: 120 KDa

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Macromolecule #1: Synaptic vesicle glycoprotein 2B

MacromoleculeName: Synaptic vesicle glycoprotein 2B / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 77.515016 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MDDYKYQDNY GGYAPSDGYY RGNESNPEED AQSDVTEGHD EEDEIYEGEY QGIPHPDDVK AKQAKMAPSR MDSLRGQTDL MAERLEDEE QLAHQYETIM DECGHGRFQW ILFFVLGLAL MADGVEVFVV SFALPSAEKD MCLSSSKKGM LGMIVYLGMM A GAFILGGL ...String:
MDDYKYQDNY GGYAPSDGYY RGNESNPEED AQSDVTEGHD EEDEIYEGEY QGIPHPDDVK AKQAKMAPSR MDSLRGQTDL MAERLEDEE QLAHQYETIM DECGHGRFQW ILFFVLGLAL MADGVEVFVV SFALPSAEKD MCLSSSKKGM LGMIVYLGMM A GAFILGGL ADKLGRKRVL SMSLAVNASF ASLSSFVQGY GAFLFCRLIS GIGIGGALPI VFAYFSEFLS REKRGEHLSW LG IFWMTGG LYASAMAWSI IPHYGWGFSM GTNYHFHSWR VFVIVCALPC TVSMVALKFM PESPRFLLEM GKHDEAWMIL KQV HDTNMR AKGTPEKVFT VSNIKTPKQM DEFIEIQSST GTWYQRWLVR FKTIFKQVWD NALYCVMGPY RMNTLILAVV WFAM AFSYY GLTVWFPDMI RYFQDEEYKS KMKVFFGEHV YGATINFTME NQIHQHGKLV NDKFTRMYFK HVLFEDTFFD ECYFE DVTS TDTYFKNCTI ESTIFYNTDL YEHKFINCRF INSTFLEQKE GCHMDLEQDN DFLIYLVSFL GSLSVLPGNI ISALLM DRI GRLKMIGGSM LISAVCCFFL FFGNSESAMI GWQCLFCGTS IAAWNALDVI TVELYPTNQR ATAFGILNGL CKFGAIL GN TIFASFVGIT KVVPILLAAA SLVGGGLIAL RLPETREQVL M

UniProtKB: Synaptic vesicle glycoprotein 2B

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Macromolecule #2: Botulinum neurotoxin A heavy chain

MacromoleculeName: Botulinum neurotoxin A heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Clostridium botulinum (bacteria)
Molecular weightTheoretical: 51.724617 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MKKHHHHHHG SLVPRGSKNI INTSILNLRY ESNHLIDLSR YASKINIGSK VNFDPIDKNQ IQLFNLESSK IEVILKNAIV YNSMYENFS TSFWIRIPKY FNSISLNNEY TIINCMENNS GWKVSLNYGE IIWTLQDTQE IKQRVVFKYS QMINISDYIN R WIFVTITN ...String:
MKKHHHHHHG SLVPRGSKNI INTSILNLRY ESNHLIDLSR YASKINIGSK VNFDPIDKNQ IQLFNLESSK IEVILKNAIV YNSMYENFS TSFWIRIPKY FNSISLNNEY TIINCMENNS GWKVSLNYGE IIWTLQDTQE IKQRVVFKYS QMINISDYIN R WIFVTITN NRLNNSKIYI NGRLIDQKPI SNLGNIHASN NIMFKLDGCR DTHRYIWIKY FNLFDKELNE KEIKDLYDNQ SN SGILKDF WGDYLQYDKP YYMLNLYDPN KYVDVNNVGI RGYMYLKGPR GSVMTTNIYL NSSLYRGTKF IIKKYASGNK DNI VRNNDR VYINVVVKNK EYRLATNASQ AGVEKILSAL EIPDVGNLSQ VVVMKSKNDQ GITNKCKMNL QDNNGNDIGF IGFH QFNNI AKLVASNWYN RQIERSSRTL GCSWEFIPVD DGWGERPL

UniProtKB: Botulinum neurotoxin type A

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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: 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

BufferpH: 8
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / 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 / Nominal defocus max: 2.4 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.67 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 185478
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial model
PDB IDChain

2-f1

source_name: AlphaFold, initial_model_type: in silico model

2vu9

source_name: PDB, initial_model_type: experimental model
RefinementProtocol: RIGID BODY FIT
Output model

PDB-9f1r:
Cryo-EM structure of SV2B-Hc-A1 complex

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