---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '19846'
abstract:
- lang: eng
  text: The Ca2+-release-activated Ca2+ (CRAC) channel Orai1 is activated by interaction
    with the Ca2+ sensor Stromal Interaction Molecule 1 (STIM1). Owing to the lack
    of structurally resolved Orai1/STIM1 complexes, the impact of their coupling on
    individual Orai1 transmembrane domain (TM) movements is unclear. This study investigates
    STIM1-independent and STIM1-dependent Orai1-TM dynamics using photocrosslinking
    unnatural amino acids (UAAs) at each individual TM position. We primarily identify
    CRAC-channel-like currents directly after UAA incorporation or additional UV-light
    irradiation at TM3 sites that interface with non-pore-lining TMs. Using UAAs combined
    with conventional site-directed mutagenesis and molecular dynamics simulations,
    we discover that pore opening involves a widening of interfaces formed by TM3
    with non-pore-lining TMs. Orai1 mutants with a UAA in TM3 exhibit weaker STIM1-induced
    activation after UV exposure, possibly caused by a restricted widening of non-pore-lining
    TM interfaces. We demonstrate that photocrosslinking UAAs are excellent tools
    for improving our understanding of key determinants and ion channel dynamics modulating
    pore opening.
acknowledgement: We thank S. Buchegger for excellent technical assistance. This research
  was funded by the Austrian Science Fund (FWF) projects https://doi.org/10.55776/P32851,
  https://doi.org/10.55776/P35900, and https://doi.org/10.55776/P36202 to I.D. and
  https://doi.org/10.55776/PAT6871323 to A.T. N.M. is funded within the DOC program
  of the OeAW (Austrian Academy of Science). For open access purposes, the author
  has applied a CC BY public copyright license to any author-accepted manuscript version
  arising from this submission.
article_number: '102623'
article_processing_charge: Yes
article_type: original
author:
- first_name: Hadil
  full_name: Najjar, Hadil
  last_name: Najjar
- first_name: Sarah
  full_name: Weiß, Sarah
  last_name: Weiß
- first_name: Ferdinand
  full_name: Horvath, Ferdinand
  id: b0dc7f61-21a3-11ef-a9b4-e6ab1aa6f21e
  last_name: Horvath
- first_name: Valentina
  full_name: Hopl, Valentina
  last_name: Hopl
- first_name: Adéla
  full_name: Tiffner, Adéla
  last_name: Tiffner
- first_name: Lorenz
  full_name: Höbarth, Lorenz
  last_name: Höbarth
- first_name: Julia
  full_name: Söllner, Julia
  last_name: Söllner
- first_name: Maximilian
  full_name: Fröhlich, Maximilian
  last_name: Fröhlich
- first_name: Magdalena
  full_name: Prantl, Magdalena
  last_name: Prantl
- first_name: Nora
  full_name: Müller, Nora
  last_name: Müller
- first_name: Yuliia
  full_name: Nazarenko, Yuliia
  last_name: Nazarenko
- first_name: Selina
  full_name: Harant, Selina
  last_name: Harant
- first_name: Lukas
  full_name: Weissenböck, Lukas
  last_name: Weissenböck
- first_name: Herwig
  full_name: Grabmayr, Herwig
  last_name: Grabmayr
- first_name: Matthias
  full_name: Sallinger, Matthias
  last_name: Sallinger
- first_name: Lena
  full_name: Maltan, Lena
  last_name: Maltan
- first_name: Linda V.
  full_name: Echefu, Linda V.
  last_name: Echefu
- first_name: Tamara
  full_name: Radiskovic, Tamara
  last_name: Radiskovic
- first_name: Melanie
  full_name: Leopold, Melanie
  last_name: Leopold
- first_name: Sonja
  full_name: Lindinger, Sonja
  last_name: Lindinger
- first_name: Christina
  full_name: Humer, Christina
  last_name: Humer
- first_name: Carmen
  full_name: Höglinger, Carmen
  last_name: Höglinger
- first_name: Heinrich
  full_name: Krobath, Heinrich
  last_name: Krobath
- first_name: Thomas
  full_name: Renger, Thomas
  last_name: Renger
- first_name: Isabella
  full_name: Derler, Isabella
  last_name: Derler
citation:
  ama: Najjar H, Weiß S, Horvath F, et al. STIM1-induced widening of non-pore-lining
    TM interfaces is crucial for Orai1 pore opening. <i>Cell Reports Physical Science</i>.
    2025;6(6). doi:<a href="https://doi.org/10.1016/j.xcrp.2025.102623">10.1016/j.xcrp.2025.102623</a>
  apa: Najjar, H., Weiß, S., Horvath, F., Hopl, V., Tiffner, A., Höbarth, L., … Derler,
    I. (2025). STIM1-induced widening of non-pore-lining TM interfaces is crucial
    for Orai1 pore opening. <i>Cell Reports Physical Science</i>. Elsevier. <a href="https://doi.org/10.1016/j.xcrp.2025.102623">https://doi.org/10.1016/j.xcrp.2025.102623</a>
  chicago: Najjar, Hadil, Sarah Weiß, Ferdinand Horvath, Valentina Hopl, Adéla Tiffner,
    Lorenz Höbarth, Julia Söllner, et al. “STIM1-Induced Widening of Non-Pore-Lining
    TM Interfaces Is Crucial for Orai1 Pore Opening.” <i>Cell Reports Physical Science</i>.
    Elsevier, 2025. <a href="https://doi.org/10.1016/j.xcrp.2025.102623">https://doi.org/10.1016/j.xcrp.2025.102623</a>.
  ieee: H. Najjar <i>et al.</i>, “STIM1-induced widening of non-pore-lining TM interfaces
    is crucial for Orai1 pore opening,” <i>Cell Reports Physical Science</i>, vol.
    6, no. 6. Elsevier, 2025.
  ista: Najjar H, Weiß S, Horvath F, Hopl V, Tiffner A, Höbarth L, Söllner J, Fröhlich
    M, Prantl M, Müller N, Nazarenko Y, Harant S, Weissenböck L, Grabmayr H, Sallinger
    M, Maltan L, Echefu LV, Radiskovic T, Leopold M, Lindinger S, Humer C, Höglinger
    C, Krobath H, Renger T, Derler I. 2025. STIM1-induced widening of non-pore-lining
    TM interfaces is crucial for Orai1 pore opening. Cell Reports Physical Science.
    6(6), 102623.
  mla: Najjar, Hadil, et al. “STIM1-Induced Widening of Non-Pore-Lining TM Interfaces
    Is Crucial for Orai1 Pore Opening.” <i>Cell Reports Physical Science</i>, vol.
    6, no. 6, 102623, Elsevier, 2025, doi:<a href="https://doi.org/10.1016/j.xcrp.2025.102623">10.1016/j.xcrp.2025.102623</a>.
  short: H. Najjar, S. Weiß, F. Horvath, V. Hopl, A. Tiffner, L. Höbarth, J. Söllner,
    M. Fröhlich, M. Prantl, N. Müller, Y. Nazarenko, S. Harant, L. Weissenböck, H.
    Grabmayr, M. Sallinger, L. Maltan, L.V. Echefu, T. Radiskovic, M. Leopold, S.
    Lindinger, C. Humer, C. Höglinger, H. Krobath, T. Renger, I. Derler, Cell Reports
    Physical Science 6 (2025).
date_created: 2025-06-15T22:01:31Z
date_published: 2025-06-18T00:00:00Z
date_updated: 2025-09-30T12:53:15Z
day: '18'
ddc:
- '570'
department:
- _id: AnSa
doi: 10.1016/j.xcrp.2025.102623
external_id:
  isi:
  - '001516570500009'
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file_date_updated: 2025-06-23T10:20:22Z
has_accepted_license: '1'
intvolume: '         6'
isi: 1
issue: '6'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '06'
oa: 1
oa_version: Published Version
publication: Cell Reports Physical Science
publication_identifier:
  eissn:
  - 2666-3864
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: STIM1-induced widening of non-pore-lining TM interfaces is crucial for Orai1
  pore opening
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 6
year: '2025'
...