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- EMDB-66467: Cryo-EM structure of Borna disease virus RNA polymerase complex -

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Basic information

Entry
Database: EMDB / ID: EMD-66467
TitleCryo-EM structure of Borna disease virus RNA polymerase complex
Map data
Sample
  • Complex: Borna disease virus RNA polymerase complex
    • Protein or peptide: RNA-directed RNA polymerase L
    • Protein or peptide: Phosphoprotein
KeywordsPolymerase / Phosphoprotein / PhosComplex / VIRAL PROTEIN
Function / homology
Function and homology information


exit of virus from host cell nucleus through nuclear pore / virion component / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / symbiont-mediated suppression of host toll-like receptor signaling pathway / host cell cytoplasm / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA-directed RNA polymerase / RNA-directed RNA polymerase activity / host cell nucleus / ATP binding
Similarity search - Function
Borna disease virus P24 / Borna disease virus P24 protein / Mononegavirales RNA-directed RNA polymerase catalytic domain / Mononegavirales mRNA-capping domain V / Mononegavirales RNA dependent RNA polymerase / Mononegavirales mRNA-capping region V / RdRp of negative ssRNA viruses with non-segmented genomes catalytic domain profile.
Similarity search - Domain/homology
Phosphoprotein / RNA-directed RNA polymerase L
Similarity search - Component
Biological speciesBorna disease virus-V
Methodsingle particle reconstruction / cryo EM / Resolution: 2.72 Å
AuthorsMa J / Yang K / Wu H / Liang Z
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell Rep / Year: 2026
Title: Structural mechanism of Borna disease virus 1 RNA polymerase autoinhibition and suramin-mediated inhibition.
Authors: Kankan Yang / Haiqiang Wu / Zuxing Liang / Junwei Zou / Jun Ma /
Abstract: Borna disease virus 1 (BoDV-1) is a neurotropic pathogen that causes severe, often fatal encephalitis, yet effective treatments remain unavailable. As a nuclear-replicating mononegavirus, BoDV-1 ...Borna disease virus 1 (BoDV-1) is a neurotropic pathogen that causes severe, often fatal encephalitis, yet effective treatments remain unavailable. As a nuclear-replicating mononegavirus, BoDV-1 employs a minimal L-P polymerase complex. Here, we report cryo-electron microscopy (cryo-EM) structures of the BoDV-1 polymerase in L-alone, apo-L-P, and inhibitor-bound L-P states, revealing the most compact L protein characterized among mononegaviruses. While the catalytic core is conserved, the C-terminal domains are degenerate, with the methyltransferase-like (MTase-like) domain lacking canonical functional motifs. We identify an N-terminal autoinhibitory element (AIE) that is positioned to physically block the template entry tunnel, suggesting an autoinhibition mechanism reminiscent of a "molecular plug." Furthermore, we demonstrate that the inhibitor suramin binds in a specific triple-molecule mode, potentially achieving inhibition by sterically occluding RNA access and allosterically restricting the catalytic core. These findings elucidate the architecture and regulation of the BoDV-1 polymerase, providing a structural framework for rational antiviral design.
History
DepositionOct 3, 2025-
Header (metadata) releaseJun 10, 2026-
Map releaseJun 10, 2026-
UpdateJun 10, 2026-
Current statusJun 10, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_66467.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.73 Å/pix.
x 320 pix.
= 233.6 Å
0.73 Å/pix.
x 320 pix.
= 233.6 Å
0.73 Å/pix.
x 320 pix.
= 233.6 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.73 Å
Density
Contour LevelBy AUTHOR: 0.015
Minimum - Maximum-0.073522784 - 0.15864787
Average (Standard dev.)-0.0000248233 (±0.005073369)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 233.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Additional map: #1

Fileemd_66467_additional_1.map
Projections & Slices
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Half map: #2

Fileemd_66467_half_map_1.map
Projections & Slices
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Half map: #1

Fileemd_66467_half_map_2.map
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Sample components

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Entire : Borna disease virus RNA polymerase complex

EntireName: Borna disease virus RNA polymerase complex
Components
  • Complex: Borna disease virus RNA polymerase complex
    • Protein or peptide: RNA-directed RNA polymerase L
    • Protein or peptide: Phosphoprotein

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Supramolecule #1: Borna disease virus RNA polymerase complex

SupramoleculeName: Borna disease virus RNA polymerase complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Borna disease virus-V
Molecular weightTheoretical: 281 KDa

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Macromolecule #1: RNA-directed RNA polymerase L

MacromoleculeName: RNA-directed RNA polymerase L / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: RNA-directed RNA polymerase
Source (natural)Organism: Borna disease virus-V
Molecular weightTheoretical: 194.970875 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: MSFHASLLRE EETPRPVAGI NRTDQSLKNP LLGTEVSFCL KSSSLPHHVR ALGQIKARNL ASCDYYLLFR QVVLPPEVYP IGVLIRAAE AILTVIVSAW KLDHMTKTLY SSVRYALTNP RVRAQLELHI AYQRIVGQVS YSREADIGPK RLGNMSLQFI Q SLVIATID ...String:
MSFHASLLRE EETPRPVAGI NRTDQSLKNP LLGTEVSFCL KSSSLPHHVR ALGQIKARNL ASCDYYLLFR QVVLPPEVYP IGVLIRAAE AILTVIVSAW KLDHMTKTLY SSVRYALTNP RVRAQLELHI AYQRIVGQVS YSREADIGPK RLGNMSLQFI Q SLVIATID TTSCLMTYNH FLAAADTAKS RCHLLIASVV QGALWEQGSF LDHIINMIDI IDSINLPHDD YFTIIKSIFP YS QGLVMGR HNVSVSSDFA SVFAIPELCP QLDSLLKKLL QLDPVLLLMV SSVQKSWYFP EIRMVDGSRE QLHKMRVELE TPQ ALLSYG HTLLSIFRAE FIKGYVSKNA KWPPVHLLPG CDKSIKNARE LGRWSPAFDR RWQLFEKVVI LRIADLDMDP DFND IVSDK AIISSRRDWV FEYNAAAFWK KYGERLERPP ARSGPSRLVN ALIDGRLDNI PALLEPFYRG AVEFEDRLTV LVPKE KELK VKGRFFSKQT LAIRIYQVVA EAALKNEVMP YLKTHSMTMS STALTHLLNR LSHTITKGDS FVINLDYSSW CNGFRP ELQ APICRQLDQM FNCGYFFRTG CTLPCFTTFI IQDRFNPPYS LSGEPVEDGV TCAVGTKTMG EGMRQKLWTI LTSCWEI IA LREINVTFNI LGQGDNQTII IHKSASQNNQ LLAERALGAL YKHARLAGHN LKVEECWVSD CLYEYGKKLF FRGVPVPG C LKQLSRVTDS TGELFPNLYS KLACLTSSCL SAAMADTSPW VALATGVCLY LIELYVELPP AIIQDESLLT TLCLVGPSI GGLPTPATLP SVFFRGMSDP LPFQLALLQT LIKTTGVTCS LVNRVVKLRI APYPDWLSLV TDPTSLNIAQ VYRPERQIRR WIEEAIATS SHSSRIATFF QQPLTEMAQL LARDLSTMMP LRPRDMSALF ALSNVAYGLS IIDLFQKSST VVSASQAVHI E DVALESVR YKESIIQGLL DTTEGYNMQP YLEGCTYLAA KQLRRLTWGR DLVGVTMPFV AEQFHPHSSV GAKAELYLDA II YCPQETL RSHHLTTRGD QPLYLGSNTA VKVQRGEITG LAKSRAANLV KDTLVLHQWY KVRKVTDPHL NTLMARFLLE KGY TSDARP SIQGGTLTHR LPSRGDSRQG LTGYVNILST WLRFSSDYLH SFSKSSDDYT IHFQHVFTYG CLYADSVIRS GGVI STPYL LSASCKTCFE KIDSEEFVLA CEPQYRGAEW LISKPVTVPE QITDAEVEFD PCVSASYCLG ILIGKSFLVD IRASG HDIM EQRTWANLER FSVSDMQKLP WSIVIRSLWR FLIGARLLQF EKAGLIRMLY AATGPTFSFL MKVFQDSALL MDCAPL DRL SPRINFHSRG DLVAKLVLLP FINPGIVEIE VSGINSKYHA VSEANMDLYI AAAKSVGVKP TQFVEETNDF TARGHHH GC YSLSWSKSRN QSQVLKMVVR KLKLCVLYIY PTVDPAVALD LCHLPALTII LVLGGDPAYY ERLLEMDLCG AVSSRVDI P HSLAARTHRG FAVGPDAGPG VIRLDRLESV CYAHPCLEEL EFNAYLDSEL VDISDMCCLP LATPCKALFR PIYRSLQSF RLALMDNYSF VMDLIMIRGL DIRPHLEEFD ELLVVGQHIL GQPVLVEVVY YVGVVRKRPV LARHPWSADL KRITVGGRAP CPSAARLRD EDCQGSLLVG LPAGLTQLLI IDWSHPQFEK GSSGGSSGSS GGAWSHPQFE K

UniProtKB: RNA-directed RNA polymerase L

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Macromolecule #2: Phosphoprotein

MacromoleculeName: Phosphoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Borna disease virus-V
Molecular weightTheoretical: 22.515633 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: MATRPSSLVD SLEDEEDPQT LRRERPGSPR PRKVPRNALT QPVDQLLKDL RKNPSMISDP DQRTGREQLS NDELIKKLVT ELAENSMIE AEEVRGTLGD ISARIEAGFE SLSALQVETI QTAQRCDHSD SIRILGENIK ILDRSMKTMM ETMKLMMEKV D LLYASTAV ...String:
MATRPSSLVD SLEDEEDPQT LRRERPGSPR PRKVPRNALT QPVDQLLKDL RKNPSMISDP DQRTGREQLS NDELIKKLVT ELAENSMIE AEEVRGTLGD ISARIEAGFE SLSALQVETI QTAQRCDHSD SIRILGENIK ILDRSMKTMM ETMKLMMEKV D LLYASTAV GTSAPMLPSH PAPPRIYPQL PSAPTTDEWD IIP

UniProtKB: Phosphoprotein

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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

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k 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: 2.5 µm / Nominal defocus min: 1.2 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: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.72 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.6) / Number images used: 300038
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
RefinementProtocol: RIGID BODY FIT
Output model

PDB-9x1v:
Cryo-EM structure of Borna disease virus RNA polymerase complex

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