Evidence map›Paper›PMID 40593561›Full record

ArticleNature communications2025

Trioxane-based MS-cleavable cross-linking mass spectrometry for profiling multimeric interactions of cellular networks.

Clinton Yu, Eric Novitsky, Sree Ganesh Balasubramani, Xiaorong Wang, Xiyu Shen, Qin Yang, Scott Rychnovsky, Ignacia Echeverria, Lan Huang

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Clinton YuDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.
Eric NovitskyDepartment of Chemistry, University of California, Irvine, Irvine, CA, USA.
Sree Ganesh BalasubramaniDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
Xiaorong WangDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.
Xiyu ShenDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0009-0005-2295-8476
Qin YangDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.
Scott RychnovskyDepartment of Chemistry, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-7223-4389
Ignacia EcheverriaDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4717-1467
Lan HuangDepartment of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA. lanhuang@uci.edu.ORCID http://orcid.org/0000-0002-3140-4687

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Epigenetic Regulation of Mitochondrial Homeostasis and Energy MetabolismR01DK121146 · NIDDK · UNIVERSITY OF CALIFORNIA-IRVINE · PI Qin Yang · 2019 to 2026
$3.5M
Supplement: Advancing Proteomics Technologies to Decipher the Ubiquitin-Proteasome SystemR35GM145249 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Lan Huang · 2022 to 2026
$3.2M
Alternative polyadenylation as a novel mechanism for diabetesR01DK136940 · NIDDK · UNIVERSITY OF CALIFORNIA-IRVINE · PI Qin Yang · 2023 to 2026
$2.9M
Structural surfaceomics to probe conformation-selective immunotherapy targetsR01CA290875 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lan Huang, Arun P. Wiita · 2024 to 2026
$2.7M
Using in vivo genetic and physical interaction data for structure determination of protein assembliesR35GM151256 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Ignacia Echeverria Riesco · 2023 to 2026
$1.6M
NCI NIH HHS P30 CA062203NCI NIH HHS R01 CA290875NIDDK NIH HHS R01 DK121146NIDDK NIH HHS R01 DK136940NIGMS NIH HHS R35 GM145249NIGMS NIH HHS R35 GM151256U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK121146U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK136940U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) 35GM151256U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM145249U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics) R01CA290875
6 · The paper itself

Abstract

Cross-linking mass spectrometry (XL-MS) is a powerful technology for mapping protein-protein interactions (PPIs) at the systems level. While bivalent cross-links are effective for defining protein interactions and structures, multivalent cross-links offer enhanced spatial resolution to facilitate characterization of heterogeneous protein complexes. However, their identification remains challenging due to fragmentation complexity and the vast expansion of database search space. Here, we present tris-succinimidyl trioxane (TSTO), a novel trioxane-based, MS-cleavable homotrifunctional cross-linker capable of targeting three proximal lysines simultaneously. TSTO's unique MS-cleavability enables concurrent release of cross-linked peptide constituents during collision-induced dissociation, permitting their unambiguous identification. The TSTO-based XL-MS platform is effective for mapping cellular networks from intact cells and tissues, illustrating its versatility for complex biological systems. Trimeric interactions captured by TSTO reveal structural details inaccessible to bifunctional reagents, enhancing modeling accuracy and precision. Furthermore, this development opens a new avenue for designing multifunctional MS-cleavable cross-linkers to further advance structural systems biology.

Indexed as

Cross-Linking ReagentsMass SpectrometryProtein Interaction MappingAnimalsHumansMiceProtein Interaction MapsSuccinimidesCross-Linking ReagentsSuccinimides

Identifiers

PMID40593561
PMCPMC12215968

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.