---
_id: '14979'
abstract:
- lang: eng
  text: Poxviruses are among the largest double-stranded DNA viruses, with members
    such as variola virus, monkeypox virus and the vaccination strain vaccinia virus
    (VACV). Knowledge about the structural proteins that form the viral core has remained
    sparse. While major core proteins have been annotated via indirect experimental
    evidence, their structures have remained elusive and they could not be assigned
    to individual core features. Hence, which proteins constitute which layers of
    the core, such as the palisade layer and the inner core wall, has remained enigmatic.
    Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach
    in combination with AlphaFold molecular modeling, that trimers formed by the cleavage
    product of VACV protein A10 are the key component of the palisade layer. This
    allows us to place previously obtained descriptions of protein interactions within
    the core wall into perspective and to provide a detailed model of poxvirus core
    architecture. Importantly, we show that interactions within A10 trimers are likely
    generalizable over members of orthopox- and parapoxviruses.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: EM-Fac
acknowledgement: "We thank A. Bergthaler (Research Center for Molecular Medicine of
  the Austrian Academy of Sciences) for providing VACV WR. We thank A. Nicholas and
  his team at the ISTA proteomics facility, and S. Elefante at the ISTA Scientific
  Computing facility for their support. We also thank F. Fäßler, D. Porley, T. Muthspiel
  and other members of the Schur group for support and helpful discussions. We also
  thank D. Castaño-Díez for support with Dynamo. We thank D. Farrell for his help
  optimizing the Rosetta protocol to refine the atomic model into the cryo-EM map
  with symmetry.\r\n\r\nF.K.M.S. acknowledges support from ISTA and EMBO. F.K.M.S.
  also received support from the Austrian Science Fund (FWF) grant P31445. This publication
  has been made possible in part by CZI grant DAF2021-234754 and grant https://doi.org/10.37921/812628ebpcwg
  from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community
  Foundation (funder https://doi.org/10.13039/100014989) awarded to F.K.M.S.\r\n\r\nThis
  research was also supported by the Scientific Service Units (SSUs) of ISTA through
  resources provided by Scientific Computing (SciComp), the Life Science Facility
  (LSF), and the Electron Microscopy Facility (EMF). We also acknowledge the use of
  COSMIC45 and Colabfold46."
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia
  full_name: Datler, Julia
  id: 3B12E2E6-F248-11E8-B48F-1D18A9856A87
  last_name: Datler
  orcid: 0000-0002-3616-8580
- first_name: Jesse
  full_name: Hansen, Jesse
  id: 1063c618-6f9b-11ec-9123-f912fccded63
  last_name: Hansen
- first_name: Andreas
  full_name: Thader, Andreas
  id: 3A18A7B8-F248-11E8-B48F-1D18A9856A87
  last_name: Thader
- first_name: Alois
  full_name: Schlögl, Alois
  id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
  last_name: Schlögl
  orcid: 0000-0002-5621-8100
- first_name: Lukas W
  full_name: Bauer, Lukas W
  id: 0c894dcf-897b-11ed-a09c-8186353224b0
  last_name: Bauer
- first_name: Victor-Valentin
  full_name: Hodirnau, Victor-Valentin
  id: 3661B498-F248-11E8-B48F-1D18A9856A87
  last_name: Hodirnau
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
citation:
  ama: Datler J, Hansen J, Thader A, et al. Multi-modal cryo-EM reveals trimers of
    protein A10 to form the palisade layer in poxvirus cores. <i>Nature Structural
    &#38; Molecular Biology</i>. 2024. doi:<a href="https://doi.org/10.1038/s41594-023-01201-6">10.1038/s41594-023-01201-6</a>
  apa: Datler, J., Hansen, J., Thader, A., Schlögl, A., Bauer, L. W., Hodirnau, V.-V.,
    &#38; Schur, F. K. (2024). Multi-modal cryo-EM reveals trimers of protein A10
    to form the palisade layer in poxvirus cores. <i>Nature Structural &#38; Molecular
    Biology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41594-023-01201-6">https://doi.org/10.1038/s41594-023-01201-6</a>
  chicago: Datler, Julia, Jesse Hansen, Andreas Thader, Alois Schlögl, Lukas W Bauer,
    Victor-Valentin Hodirnau, and Florian KM Schur. “Multi-Modal Cryo-EM Reveals Trimers
    of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural
    &#38; Molecular Biology</i>. Springer Nature, 2024. <a href="https://doi.org/10.1038/s41594-023-01201-6">https://doi.org/10.1038/s41594-023-01201-6</a>.
  ieee: J. Datler <i>et al.</i>, “Multi-modal cryo-EM reveals trimers of protein A10
    to form the palisade layer in poxvirus cores,” <i>Nature Structural &#38; Molecular
    Biology</i>. Springer Nature, 2024.
  ista: Datler J, Hansen J, Thader A, Schlögl A, Bauer LW, Hodirnau V-V, Schur FK.
    2024. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade
    layer in poxvirus cores. Nature Structural &#38; Molecular Biology.
  mla: Datler, Julia, et al. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to
    Form the Palisade Layer in Poxvirus Cores.” <i>Nature Structural &#38; Molecular
    Biology</i>, Springer Nature, 2024, doi:<a href="https://doi.org/10.1038/s41594-023-01201-6">10.1038/s41594-023-01201-6</a>.
  short: J. Datler, J. Hansen, A. Thader, A. Schlögl, L.W. Bauer, V.-V. Hodirnau,
    F.K. Schur, Nature Structural &#38; Molecular Biology (2024).
date_created: 2024-02-12T09:59:45Z
date_published: 2024-02-05T00:00:00Z
date_updated: 2024-03-05T09:27:47Z
day: '05'
ddc:
- '570'
department:
- _id: FlSc
- _id: ScienComp
- _id: EM-Fac
doi: 10.1038/s41594-023-01201-6
external_id:
  pmid:
  - '38316877'
has_accepted_license: '1'
keyword:
- Molecular Biology
- Structural Biology
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41594-023-01201-6
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 26736D6A-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P31445
  name: Structural conservation and diversity in retroviral capsid
publication: Nature Structural & Molecular Biology
publication_identifier:
  eissn:
  - 1545-9985
  issn:
  - 1545-9993
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA Website
    relation: press_release
    url: https://ista.ac.at/en/news/down-to-the-core-of-poxviruses/
status: public
title: Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer
  in poxvirus cores
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
_id: '12334'
abstract:
- lang: eng
  text: Regulation of the Arp2/3 complex is required for productive nucleation of
    branched actin networks. An emerging aspect of regulation is the incorporation
    of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit
    isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity
    and branch junction stability. We have combined reverse genetics and cellular
    structural biology to describe how ArpC5 and ArpC5L differentially affect cell
    migration. Both define the structural stability of ArpC1 in branch junctions and,
    in turn, by determining protrusion characteristics, affect protein dynamics and
    actin network ultrastructure. ArpC5 isoforms also affect the positioning of members
    of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament
    elongators, which mediate ArpC5 isoform–specific effects on the actin assembly
    level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling
    pathway enhancing cell migration.</jats:p>
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: Bio
- _id: EM-Fac
acknowledgement: "We would like to thank K. von Peinen and B. Denker (Helmholtz Centre
  for Infection Research, Braunschweig, Germany) for experimental and technical assistance,
  respectively.\r\nThis research was supported by the Scientific Service Units (SSUs)
  of ISTA through resources provided by Scientific Computing (SciComp), the Life Science
  Facility (LSF), the Imaging and Optics facility (IOF), and the Electron Microscopy
  Facility (EMF). We acknowledge support from ISTA and from the Austrian Science Fund
  (FWF) (P33367) to F.K.M.S., from the Research Training Group GRK2223 and the Helmholtz
  Society to K.R,. and from the Deutsche Forschungsgemeinschaft (DFG) to J.F. and
  K.R."
article_number: add6495
article_processing_charge: No
article_type: original
author:
- first_name: Florian
  full_name: Fäßler, Florian
  id: 404F5528-F248-11E8-B48F-1D18A9856A87
  last_name: Fäßler
  orcid: 0000-0001-7149-769X
- first_name: Manjunath
  full_name: Javoor, Manjunath
  id: 305ab18b-dc7d-11ea-9b2f-b58195228ea2
  last_name: Javoor
- first_name: Julia
  full_name: Datler, Julia
  id: 3B12E2E6-F248-11E8-B48F-1D18A9856A87
  last_name: Datler
  orcid: 0000-0002-3616-8580
- first_name: Hermann
  full_name: Döring, Hermann
  last_name: Döring
- first_name: Florian
  full_name: Hofer, Florian
  id: b9d234ba-9e33-11ed-95b6-cd561df280e6
  last_name: Hofer
- first_name: Georgi A
  full_name: Dimchev, Georgi A
  id: 38C393BE-F248-11E8-B48F-1D18A9856A87
  last_name: Dimchev
  orcid: 0000-0001-8370-6161
- first_name: Victor-Valentin
  full_name: Hodirnau, Victor-Valentin
  id: 3661B498-F248-11E8-B48F-1D18A9856A87
  last_name: Hodirnau
- first_name: Jan
  full_name: Faix, Jan
  last_name: Faix
- first_name: Klemens
  full_name: Rottner, Klemens
  last_name: Rottner
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
citation:
  ama: Fäßler F, Javoor M, Datler J, et al. ArpC5 isoforms regulate Arp2/3 complex–dependent
    protrusion through differential Ena/VASP positioning. <i>Science Advances</i>.
    2023;9(3). doi:<a href="https://doi.org/10.1126/sciadv.add6495">10.1126/sciadv.add6495</a>
  apa: Fäßler, F., Javoor, M., Datler, J., Döring, H., Hofer, F., Dimchev, G. A.,
    … Schur, F. K. (2023). ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion
    through differential Ena/VASP positioning. <i>Science Advances</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.add6495">https://doi.org/10.1126/sciadv.add6495</a>
  chicago: Fäßler, Florian, Manjunath Javoor, Julia Datler, Hermann Döring, Florian
    Hofer, Georgi A Dimchev, Victor-Valentin Hodirnau, Jan Faix, Klemens Rottner,
    and Florian KM Schur. “ArpC5 Isoforms Regulate Arp2/3 Complex–Dependent Protrusion
    through Differential Ena/VASP Positioning.” <i>Science Advances</i>. American
    Association for the Advancement of Science, 2023. <a href="https://doi.org/10.1126/sciadv.add6495">https://doi.org/10.1126/sciadv.add6495</a>.
  ieee: F. Fäßler <i>et al.</i>, “ArpC5 isoforms regulate Arp2/3 complex–dependent
    protrusion through differential Ena/VASP positioning,” <i>Science Advances</i>,
    vol. 9, no. 3. American Association for the Advancement of Science, 2023.
  ista: Fäßler F, Javoor M, Datler J, Döring H, Hofer F, Dimchev GA, Hodirnau V-V,
    Faix J, Rottner K, Schur FK. 2023. ArpC5 isoforms regulate Arp2/3 complex–dependent
    protrusion through differential Ena/VASP positioning. Science Advances. 9(3),
    add6495.
  mla: Fäßler, Florian, et al. “ArpC5 Isoforms Regulate Arp2/3 Complex–Dependent Protrusion
    through Differential Ena/VASP Positioning.” <i>Science Advances</i>, vol. 9, no.
    3, add6495, American Association for the Advancement of Science, 2023, doi:<a
    href="https://doi.org/10.1126/sciadv.add6495">10.1126/sciadv.add6495</a>.
  short: F. Fäßler, M. Javoor, J. Datler, H. Döring, F. Hofer, G.A. Dimchev, V.-V.
    Hodirnau, J. Faix, K. Rottner, F.K. Schur, Science Advances 9 (2023).
date_created: 2023-01-23T07:26:42Z
date_published: 2023-01-20T00:00:00Z
date_updated: 2023-11-21T08:05:35Z
day: '20'
ddc:
- '570'
department:
- _id: FlSc
- _id: EM-Fac
doi: 10.1126/sciadv.add6495
external_id:
  isi:
  - '000964550100015'
file:
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  creator: dernst
  date_created: 2023-01-23T07:45:54Z
  date_updated: 2023-01-23T07:45:54Z
  file_id: '12335'
  file_name: 2023_ScienceAdvances_Faessler.pdf
  file_size: 1756234
  relation: main_file
  success: 1
file_date_updated: 2023-01-23T07:45:54Z
has_accepted_license: '1'
intvolume: '         9'
isi: 1
issue: '3'
keyword:
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language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
project:
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  grant_number: P33367
  name: Structure and isoform diversity of the Arp2/3 complex
publication: Science Advances
publication_identifier:
  issn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
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    relation: research_data
    status: public
scopus_import: '1'
status: public
title: ArpC5 isoforms regulate Arp2/3 complex–dependent protrusion through differential
  Ena/VASP positioning
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2023'
...