---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21929'
abstract:
- lang: eng
  text: 'The import of proteins into mitochondria poses fundamental mechanistic challenges:
    aggregation-prone precursor proteins must be maintained in aqueous compartments
    and threaded through narrow pores without becoming stuck or mislocalized. Recent
    evidence from mitochondrial protein import studies and other chaperone systems
    underscores the critical role of dynamics in balancing sufficiently tight binding,
    promiscuity, specificity, and release. Dynamic binding of client precursor proteins
    to import machinery components arises naturally from the avidity of their interactions.
    Conformational entropy enhances their stability, while the multivalent nature
    of these interactions ensures that client transfer to downstream insertases occurs
    without a substantial energy barrier. Here, we discuss this emerging paradigm
    of dynamic protein handling, using examples where dynamic structures have been
    resolved and highlight outstanding questions.'
acknowledgement: We gratefully acknowledge research funding by the Austrian Science
  Fund (FWF), projects 10.55776/PAT1647625 and 10.55776/I6223. We thank Prof. Long
  Li (Peking University) for providing structural models and EM density for the TOM
  and TIM23 complexes, used to generate part of Figure 3. Open Access funding provided
  by Institute of Science and Technology Austria.
article_number: e70630
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Jakob
  full_name: Schneider, Jakob
  id: 64368429-eb97-11eb-a6c2-c980b1f44415
  last_name: Schneider
- first_name: Undina
  full_name: Guillerm, Undina
  id: bb74f472-ae54-11eb-9835-bc9c22fb1183
  last_name: Guillerm
- first_name: Caroline
  full_name: Simoes Pereira, Caroline
  id: 87266c4a-96d2-11ef-be2c-fe5633233ec3
  last_name: Simoes Pereira
- first_name: Paul
  full_name: Schanda, Paul
  id: 7B541462-FAF6-11E9-A490-E8DFE5697425
  last_name: Schanda
  orcid: 0000-0002-9350-7606
citation:
  ama: Schneider J, Guillerm U, Simoes Pereira C, Schanda P. Dynamic disorder is crucial
    for mitochondrial protein import. <i>Protein Science</i>. 2026;35(6). doi:<a href="https://doi.org/10.1002/pro.70630">10.1002/pro.70630</a>
  apa: Schneider, J., Guillerm, U., Simoes Pereira, C., &#38; Schanda, P. (2026).
    Dynamic disorder is crucial for mitochondrial protein import. <i>Protein Science</i>.
    Wiley. <a href="https://doi.org/10.1002/pro.70630">https://doi.org/10.1002/pro.70630</a>
  chicago: Schneider, Jakob, Undina Guillerm, Caroline Simoes Pereira, and Paul Schanda.
    “Dynamic Disorder Is Crucial for Mitochondrial Protein Import.” <i>Protein Science</i>.
    Wiley, 2026. <a href="https://doi.org/10.1002/pro.70630">https://doi.org/10.1002/pro.70630</a>.
  ieee: J. Schneider, U. Guillerm, C. Simoes Pereira, and P. Schanda, “Dynamic disorder
    is crucial for mitochondrial protein import,” <i>Protein Science</i>, vol. 35,
    no. 6. Wiley, 2026.
  ista: Schneider J, Guillerm U, Simoes Pereira C, Schanda P. 2026. Dynamic disorder
    is crucial for mitochondrial protein import. Protein Science. 35(6), e70630.
  mla: Schneider, Jakob, et al. “Dynamic Disorder Is Crucial for Mitochondrial Protein
    Import.” <i>Protein Science</i>, vol. 35, no. 6, e70630, Wiley, 2026, doi:<a href="https://doi.org/10.1002/pro.70630">10.1002/pro.70630</a>.
  short: J. Schneider, U. Guillerm, C. Simoes Pereira, P. Schanda, Protein Science
    35 (2026).
corr_author: '1'
date_created: 2026-05-31T22:02:12Z
date_published: 2026-06-01T00:00:00Z
date_updated: 2026-06-02T07:26:34Z
day: '01'
ddc:
- '572'
department:
- _id: GradSch
- _id: PaSc
doi: 10.1002/pro.70630
external_id:
  pmid:
  - '42159315'
file:
- access_level: open_access
  checksum: e0163459a7238fdcc3fc5e17bedcce9a
  content_type: application/pdf
  creator: dernst
  date_created: 2026-06-02T07:23:12Z
  date_updated: 2026-06-02T07:23:12Z
  file_id: '21937'
  file_name: 2026_ProteinScience_Schneider.pdf
  file_size: 3897305
  relation: main_file
  success: 1
file_date_updated: 2026-06-02T07:23:12Z
has_accepted_license: '1'
intvolume: '        35'
issue: '6'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: bdb9578d-d553-11ed-ba76-ed5d39fce6f0
  grant_number: I06223
  name: Structure and mechanism of the mitochondrial MIM insertase
publication: Protein Science
publication_identifier:
  eissn:
  - 1469-896X
  issn:
  - 0961-8368
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dynamic disorder is crucial for mitochondrial protein import
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: 35
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20538'
abstract:
- lang: eng
  text: In this study, we describe an integrated approach for methyl group assignment
    comprising precursor-based selective methyl group labeling, a novel pulse sequence
    for methyl to backbone coherence transfer and chemical shift predictions using
    UCBShift 2.0. The utility of this novel α-ketoacid isotopologue is shown by the
    adaptation of an HMBC-HMQC pulse sequence that simultaneously connects geminal
    methyl groups of leucine and valine residues to each other and to the protein
    backbone. By additional 13C,2H-labeling of residues other than valine and leucine
    residues of the protein, important chemical shift information about neighboring
    residues (following valine and leucine residues) can be achieved. Thus, different
    valine and leucine residues in a protein can be characterized as a specific chemical
    shift vector. Frequency matching with predicted chemical shifts via UCBShift 2.0
    using experimental data taken from a subset of the BMRB database revealed a correct
    assignment performance of about 90%. With applications to proteins of 60.2 kDa
    and 134 kDa (4 × 33.5 kDa) in size, we demonstrate that the approach provides
    valuable information even for very large proteins.
acknowledged_ssus:
- _id: NMR
- _id: LifeSc
acknowledgement: A.L.P and G.T were funded by the “New Ideas” program by Vienna Doctoral
  School in Chemistry. S.K. was funded by the Austrian Science Fund FWF P35098-B.
  This work was supported financially by the Austrian Science Fund (FWF, grant numbers
  I06223 and I5812-B, “AlloSpace”). This research was supported by the Scientific
  Service Units (SSU) of Institute of Science and Technology Austria (ISTA) through
  resources provided by the Nuclear Magnetic Resonance Facility and the Lab Support
  Facility (LSF). We thank Celina Sailer for assistance with the analysis of the NMR
  spectrum of HsTom70.
article_number: '169465'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Sonja
  full_name: Knödlstorfer, Sonja
  last_name: Knödlstorfer
- first_name: Giorgia
  full_name: Toscano, Giorgia
  id: 334a5e40-8747-11f0-b671-ba1f5154b4b4
  last_name: Toscano
- first_name: Aleksandra L.
  full_name: Ptaszek, Aleksandra L.
  last_name: Ptaszek
- first_name: Georg
  full_name: Kontaxis, Georg
  last_name: Kontaxis
- first_name: Federico
  full_name: Napoli, Federico
  id: d42e08e7-f4fc-11eb-af0a-d71e26138f1b
  last_name: Napoli
  orcid: 0000-0002-9043-136X
- first_name: Jakob
  full_name: Schneider, Jakob
  id: 64368429-eb97-11eb-a6c2-c980b1f44415
  last_name: Schneider
- first_name: Katharina
  full_name: Maier, Katharina
  last_name: Maier
- first_name: Anna
  full_name: Kapitonova, Anna
  id: 9fb2a840-89e1-11ee-a8b7-cc5c7ba62471
  last_name: Kapitonova
- first_name: Roman J.
  full_name: Lichtenecker, Roman J.
  last_name: Lichtenecker
- first_name: Paul
  full_name: Schanda, Paul
  id: 7B541462-FAF6-11E9-A490-E8DFE5697425
  last_name: Schanda
  orcid: 0000-0002-9350-7606
- first_name: Robert
  full_name: Konrat, Robert
  last_name: Konrat
citation:
  ama: Knödlstorfer S, Toscano G, Ptaszek AL, et al. A novel HMBC-CC-HMQC NMR strategy
    for methyl assignment using triple-13C-labeled α-ketoisovalerate integrated with
    UCBShift 2.0. <i>Journal of Molecular Biology</i>. 2025;437(23). doi:<a href="https://doi.org/10.1016/j.jmb.2025.169465">10.1016/j.jmb.2025.169465</a>
  apa: Knödlstorfer, S., Toscano, G., Ptaszek, A. L., Kontaxis, G., Napoli, F., Schneider,
    J., … Konrat, R. (2025). A novel HMBC-CC-HMQC NMR strategy for methyl assignment
    using triple-13C-labeled α-ketoisovalerate integrated with UCBShift 2.0. <i>Journal
    of Molecular Biology</i>. Elsevier. <a href="https://doi.org/10.1016/j.jmb.2025.169465">https://doi.org/10.1016/j.jmb.2025.169465</a>
  chicago: Knödlstorfer, Sonja, Giorgia Toscano, Aleksandra L. Ptaszek, Georg Kontaxis,
    Federico Napoli, Jakob Schneider, Katharina Maier, et al. “A Novel HMBC-CC-HMQC
    NMR Strategy for Methyl Assignment Using Triple-13C-Labeled α-Ketoisovalerate
    Integrated with UCBShift 2.0.” <i>Journal of Molecular Biology</i>. Elsevier,
    2025. <a href="https://doi.org/10.1016/j.jmb.2025.169465">https://doi.org/10.1016/j.jmb.2025.169465</a>.
  ieee: S. Knödlstorfer <i>et al.</i>, “A novel HMBC-CC-HMQC NMR strategy for methyl
    assignment using triple-13C-labeled α-ketoisovalerate integrated with UCBShift
    2.0,” <i>Journal of Molecular Biology</i>, vol. 437, no. 23. Elsevier, 2025.
  ista: Knödlstorfer S, Toscano G, Ptaszek AL, Kontaxis G, Napoli F, Schneider J,
    Maier K, Kapitonova A, Lichtenecker RJ, Schanda P, Konrat R. 2025. A novel HMBC-CC-HMQC
    NMR strategy for methyl assignment using triple-13C-labeled α-ketoisovalerate
    integrated with UCBShift 2.0. Journal of Molecular Biology. 437(23), 169465.
  mla: Knödlstorfer, Sonja, et al. “A Novel HMBC-CC-HMQC NMR Strategy for Methyl Assignment
    Using Triple-13C-Labeled α-Ketoisovalerate Integrated with UCBShift 2.0.” <i>Journal
    of Molecular Biology</i>, vol. 437, no. 23, 169465, Elsevier, 2025, doi:<a href="https://doi.org/10.1016/j.jmb.2025.169465">10.1016/j.jmb.2025.169465</a>.
  short: S. Knödlstorfer, G. Toscano, A.L. Ptaszek, G. Kontaxis, F. Napoli, J. Schneider,
    K. Maier, A. Kapitonova, R.J. Lichtenecker, P. Schanda, R. Konrat, Journal of
    Molecular Biology 437 (2025).
date_created: 2025-10-26T23:01:35Z
date_published: 2025-12-01T00:00:00Z
date_updated: 2026-08-13T14:19:02Z
day: '01'
ddc:
- '540'
department:
- _id: PaSc
- _id: GradSch
doi: 10.1016/j.jmb.2025.169465
external_id:
  pmid:
  - '41016549'
file:
- access_level: open_access
  checksum: feb92f9c79032c261165f4ca573f444a
  content_type: application/pdf
  creator: dernst
  date_created: 2025-12-30T10:29:08Z
  date_updated: 2025-12-30T10:29:08Z
  file_id: '20915'
  file_name: 2025_JourMolecularBiology_Knoedlstorfer.pdf
  file_size: 3076611
  relation: main_file
  success: 1
file_date_updated: 2025-12-30T10:29:08Z
has_accepted_license: '1'
intvolume: '       437'
issue: '23'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: bdb9578d-d553-11ed-ba76-ed5d39fce6f0
  grant_number: I06223
  name: Structure and mechanism of the mitochondrial MIM insertase
- _id: eb9c82eb-77a9-11ec-83b8-aadd536561cf
  grant_number: I05812
  name: AlloSpace. The emergence and mechanisms of allostery
publication: Journal of Molecular Biology
publication_identifier:
  eissn:
  - 1089-8638
  issn:
  - 0022-2836
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A novel HMBC-CC-HMQC NMR strategy for methyl assignment using triple-13C-labeled
  α-ketoisovalerate integrated with UCBShift 2.0
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: 437
year: '2025'
...