{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:14:31Z","timestamp":1788333271957,"version":"build-2803163510"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2024ZD0530100"],"award-info":[{"award-number":["2024ZD0530100"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32401236"],"award-info":[{"award-number":["32401236"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82225041"],"award-info":[{"award-number":["82225041"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071435"],"award-info":[{"award-number":["32071435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"\u5317 \u4eac \u5e02 \u79d1 \u5b66 \u6280 \u672f \u59d4 \u5458 \u4f1a| Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["Z230020"],"award-info":[{"award-number":["Z230020"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Beijing Municipal Government"},{"DOI":"10.13039\/501100004147","name":"Tsinghua University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Syst Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cross-linking mass spectrometry is a powerful method for structural analysis, but\u00a0choosing between\u00a0cleavable and non-cleavable\u00a0cross-linkers\u00a0remains challenging. We rigorously compared non-cleavable DSS with cleavable DSSO and found that\u00a0DSS consistently yields more cross-link identifications from isolated protein complexes to bacterial lysates. The advantage of DSS diminishes as sample complexity increases. At the highest complexity tested\u2014human cell lysate\u2014the trend reverses, with DSSO outperforming DSS.\u00a0The superior performance of DSS in\u00a0less complex samples\u00a0is likely\u00a0explained by its longer and more flexible spacer arm, which interrogates a spatial volume &gt;40% larger than that of DSSO. For both\u00a0cross-linkers, the number of\u00a0identified cross-links decreases as the search space expands, but more steeply for DSS. This sharper decline arises from DSS cross-links\u00a0producing slightly lower fragment ion coverage, not from\u00a0the absence of signature ions that could reduce search space. Fragment ion coverage is key to interactome mapping: when coverage reaches 85% or above, identification sensitivity hardly decreases as the search space expands, regardless of the cross-linker used. In summary, we recommend DSS\u00a0for samples no more complex than bacterial lysates. For interactome mapping of mammalian cells, although DSSO outperforms DSS, neither achieves deep interactome coverage.<\/jats:p>","DOI":"10.1038\/s44320-026-00222-9","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:58:13Z","timestamp":1781013493000},"page":"1401-1414","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["To cleave or not to cleave: a systemic evaluation of DSS versus DSSO for cross-linking mass spectrometry analysis"],"prefix":"10.1038","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5545-1111","authenticated-orcid":false,"given":"Yong","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8363-6087","authenticated-orcid":false,"given":"Peng-Zhi","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6306-3818","authenticated-orcid":false,"given":"Qing-Cui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Lin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Cai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalet","family":"Memetimin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7139-5164","authenticated-orcid":false,"given":"Xiang-Bing","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-7194","authenticated-orcid":false,"given":"Si-Min","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6094-1182","authenticated-orcid":false,"given":"Meng-Qiu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"222_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14608-2","volume":"11","author":"R Beveridge","year":"2020","unstructured":"Beveridge R, Stadlmann J, Penninger JM, Mechtler K (2020) A synthetic peptide library for benchmarking crosslinking-mass spectrometry search engines for proteins and protein complexes. Nat Commun 11:742","journal-title":"Nat Commun"},{"key":"222_CR2","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1021\/acs.jproteome.3c00325","volume":"22","author":"MJ Birklbauer","year":"2023","unstructured":"Birklbauer MJ, Matzinger M, Muller F, Mechtler K, Dorfer V (2023) MS Annika 2.0 identifies cross-linked peptides in MS2-MS3-based workflows at high sensitivity and specificity. J Proteome Res 22:3009\u20133021","journal-title":"J Proteome Res"},{"key":"222_CR3","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1038\/s41564-023-01433-8","volume":"8","author":"B Bogdanow","year":"2023","unstructured":"Bogdanow B, Gruska I, M\u00fchlberg L, Protze J, Hohensee S, Vetter B, Bosse JB, Lehmann M, Sadeghi M, Wiebusch L et al (2023) Spatially resolved protein map of intact human cytomegalovirus virions. Nat Microbiol 8:1732\u20131747","journal-title":"Nat Microbiol"},{"key":"222_CR4","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202501845","volume":"64","author":"J Chen","year":"2025","unstructured":"Chen J, Gao H, Zhong B, Gong Z, Liu C, Zhang A, Zhao N, Chen Y, Zhao B, Liang Z et al (2025) One-step enrichment and quantitative analysis of in vivo protein complexes via dimethylpiperidine cross-linker DPST. Angew Chem Int Ed Engl 64:e202501845","journal-title":"Angew Chem Int Ed Engl"},{"key":"222_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202212860","volume":"62","author":"J Chen","year":"2023","unstructured":"Chen J, Zhao Q, Gao H, Zhao L, Chu H, Shan Y, Liang Z, Zhang Y, Zhang L (2023) A glycosidic-bond-based mass-spectrometry-cleavable cross-linker enables in vivo cross-linking for protein complex analysis. Angew Chem Int Ed Engl 62:e202212860","journal-title":"Angew Chem Int Ed Engl"},{"key":"222_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11337-z","volume":"10","author":"ZL Chen","year":"2019","unstructured":"Chen ZL, Meng JM, Cao Y, Yin JL, Fang RQ, Fan SB, Liu C, Zeng WF, Ding YH, Tan D et al (2019) A high-speed search engine pLink 2 with systematic evaluation for proteome-scale identification of cross-linked peptides. Nat Commun 10:3404","journal-title":"Nat Commun"},{"key":"222_CR7","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1038\/s41592-024-02478-1","volume":"21","author":"MA Clasen","year":"2024","unstructured":"Clasen MA, Ruwolt M, Wang C, Ruta J, Bogdanow B, Kurt LU, Zhang Z, Wang S, Gozzo FC, Chen T et al (2024) Proteome-scale recombinant standards and a robust high-speed search engine to advance cross-linking MS-based interactomics. Nat Methods 21:2327\u20132335","journal-title":"Nat Methods"},{"key":"222_CR8","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1016\/j.str.2020.07.010","volume":"28","author":"Z Gong","year":"2020","unstructured":"Gong Z, Ye SX, Tang C (2020) Tightening the crosslinking distance restraints for better resolution of protein structure and dynamics. Structure 28:1160\u20131167.e1163","journal-title":"Structure"},{"key":"222_CR9","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax5783","volume":"6","author":"MA Gonzalez-Lozano","year":"2020","unstructured":"Gonzalez-Lozano MA, Koopmans F, Sullivan PF, Protze J, Krause G, Verhage M, Li KW, Liu F, Smit AB (2020) Stitching the synapse: cross-linking mass spectrometry into resolving synaptic protein interactions. Sci Adv 6:eaax5783","journal-title":"Sci Adv"},{"key":"222_CR10","doi-asserted-by":"publisher","first-page":"10236","DOI":"10.1021\/acs.analchem.9b02372","volume":"91","author":"M Gotze","year":"2019","unstructured":"Gotze M, Iacobucci C, Ihling CH, Sinz A (2019) A simple cross-linking\/mass spectrometry workflow for studying system-wide protein interactions. Anal Chem 91:10236\u201310244","journal-title":"Anal Chem"},{"key":"222_CR11","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1021\/jacsau.4c00282","volume":"4","author":"AD Ianni","year":"2024","unstructured":"Ianni AD, Ihling CH, Vranka T, Matousek V, Sinz A, Iacobucci C (2024) Evaluating imide-based mass spectrometry-cleavable cross-linkers for structural proteomics studies. JACS Au 4:2936\u20132943","journal-title":"JACS Au"},{"key":"222_CR12","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1002\/pmic.201200352","volume":"13","author":"P Jagtap","year":"2013","unstructured":"Jagtap P, Goslinga J, Kooren JA, McGowan T, Wroblewski MS, Seymour SL, Griffin TJ (2013) A two-step database search method improves sensitivity in peptide sequence matches for metaproteomics and proteogenomics studies. Proteomics 13:1352\u20131357","journal-title":"Proteomics"},{"key":"222_CR13","doi-asserted-by":"publisher","first-page":"e202113937","DOI":"10.1002\/anie.202113937","volume":"61","author":"PL Jiang","year":"2022","unstructured":"Jiang PL, Wang C, Diehl A, Viner R, Etienne C, Nandhikonda P, Foster L, Bomgarden RD, Liu F (2022) A membrane-permeable and immobilized metal affinity chromatography (IMAC) enrichable cross-linking reagent to advance in vivo cross-linking mass spectrometry. Angew Chem Int Ed Engl 61:e202113937","journal-title":"Angew Chem Int Ed Engl"},{"key":"222_CR14","doi-asserted-by":"publisher","first-page":"4788","DOI":"10.1016\/j.cell.2022.10.030","volume":"185","author":"Z Jin","year":"2022","unstructured":"Jin Z, Wan L, Zhang Y, Li X, Cao Y, Liu H, Fan S, Cao D, Wang Z, Li X et al (2022) Structure of a TOC-TIC supercomplex spanning two chloroplast envelope membranes. Cell 185:4788\u20134800.e13","journal-title":"Cell"},{"key":"222_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11917-z","volume":"10","author":"AX Jones","year":"2019","unstructured":"Jones AX, Cao Y, Tang YL, Wang JH, Ding YH, Tan H, Chen ZL, Fang RQ, Yin J, Chen RC et al (2019) Improving mass spectrometry analysis of protein structures with arginine-selective chemical cross-linkers. Nat Commun 10:3911","journal-title":"Nat Commun"},{"key":"222_CR16","doi-asserted-by":"publisher","first-page":"M110 002212","DOI":"10.1074\/mcp.M110.002212","volume":"10","author":"A Kao","year":"2011","unstructured":"Kao A, Chiu CL, Vellucci D, Yang Y, Patel VR, Guan S, Randall A, Baldi P, Rychnovsky SD, Huang L (2011) Development of a novel cross-linking strategy for fast and accurate identification of cross-linked peptides of protein complexes. Mol Cell Proteom 10:M110 002212","journal-title":"Mol Cell Proteom"},{"key":"222_CR17","doi-asserted-by":"publisher","first-page":"7779","DOI":"10.1021\/acs.analchem.1c05266","volume":"94","author":"L Kolbowski","year":"2022","unstructured":"Kolbowski L, Lenz S, Fischer L, Sinn LR, O\u2019Reilly FJ, Rappsilber J (2022) Improved peptide backbone fragmentation is the primary advantage of MS-cleavable crosslinkers. Anal Chem 94:7779\u20137786","journal-title":"Anal Chem"},{"key":"222_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23666-z","volume":"12","author":"S Lenz","year":"2021","unstructured":"Lenz S, Sinn LR, O\u2019Reilly FJ, Fischer L, Wegner F, Rappsilber J (2021) Reliable identification of protein-protein interactions by crosslinking mass spectrometry. Nat Commun 12:3564","journal-title":"Nat Commun"},{"key":"222_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15473","volume":"8","author":"F Liu","year":"2017","unstructured":"Liu F, Lossl P, Scheltema R, Viner R, Heck AJR (2017a) Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification. Nat Commun 8:15473","journal-title":"Nat Commun"},{"key":"222_CR20","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1038\/nmeth.3603","volume":"12","author":"F Liu","year":"2015","unstructured":"Liu F, Rijkers DT, Post H, Heck AJ (2015) Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nat Methods 12:1179\u20131184","journal-title":"Nat Methods"},{"key":"222_CR21","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1016\/j.jmb.2017.03.022","volume":"429","author":"T Liu","year":"2017","unstructured":"Liu T, Dai A, Cao Y, Zhang R, Dong MQ, Wang HW (2017b) Structural insights of WHAMM\u2019s interaction with microtubules by Cryo-EM. J Mol Biol 429:1352\u20131363","journal-title":"J Mol Biol"},{"key":"222_CR22","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nmeth.3283","volume":"12","author":"S Lu","year":"2015","unstructured":"Lu S, Fan SB, Yang B, Li YX, Meng JM, Wu L, Li P, Zhang K, Zhang MJ, Fu Y et al (2015) Mapping native disulfide bonds at a proteome scale. Nat Methods 12:329\u2013331","journal-title":"Nat Methods"},{"key":"222_CR23","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1074\/mcp.RA119.001839","volume":"19","author":"KAT Makepeace","year":"2020","unstructured":"Makepeace KAT, Mohammed Y, Rudashevskaya EL, Petrotchenko EV, Vogtle FN, Meisinger C, Sickmann A, Borchers CH (2020) Improving identification of in-organello protein-protein interactions using an affinity-enrichable, isotopically coded, and mass spectrometry-cleavable chemical crosslinker. Mol Cell Proteom 19:624\u2013639","journal-title":"Mol Cell Proteom"},{"key":"222_CR24","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1021\/acs.jproteome.0c00583","volume":"20","author":"M Matzinger","year":"2021","unstructured":"Matzinger M, Mechtler K (2021) Cleavable cross-linkers and mass spectrometry for the ultimate task of profiling protein-protein interaction networks in vivo. J Proteome Res 20:78\u201393","journal-title":"J Proteome Res"},{"key":"222_CR25","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/s42004-025-01568-1","volume":"8","author":"F Muller","year":"2025","unstructured":"Muller F, Brutiu BR, Saridakis I, Leischner T, Birklbauer MJ, Matzinger M, Madalinski M, Lendl T, Shaaban S, Dorfer V et al (2025) Developing a new cleavable crosslinker reagent for in-cell crosslinking. Commun Chem 8:191","journal-title":"Commun Chem"},{"key":"222_CR26","doi-asserted-by":"publisher","first-page":"6958","DOI":"10.1021\/ac101241t","volume":"82","author":"MQ Muller","year":"2010","unstructured":"Muller MQ, Dreiocker F, Ihling CH, Schafer M, Sinz A (2010) Cleavable cross-linker for protein structure analysis: reliable identification of cross-linking products by tandem MS. Anal Chem 82:6958\u20136968","journal-title":"Anal Chem"},{"key":"222_CR27","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1126\/science.abb3758","volume":"369","author":"FJ O\u2019Reilly","year":"2020","unstructured":"O\u2019Reilly FJ, Xue L, Graziadei A, Sinn L, Lenz S, Tegunov D, Blotz C, Singh N, Hagen WJH, Cramer P et al (2020) In-cell architecture of an actively transcribing-translating expressome. Science 369:554\u2013557","journal-title":"Science"},{"key":"222_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2020.103754","volume":"220","author":"I Parfentev","year":"2020","unstructured":"Parfentev I, Schilbach S, Cramer P, Urlaub H (2020) An experimentally generated peptide database increases the sensitivity of XL-MS with complex samples. J Proteom 220:103754","journal-title":"J Proteom"},{"key":"222_CR29","doi-asserted-by":"publisher","first-page":"M110 001420","DOI":"10.1074\/mcp.M110.001420","volume":"10","author":"EV Petrotchenko","year":"2011","unstructured":"Petrotchenko EV, Serpa JJ, Borchers CH (2011) An isotopically coded CID-cleavable biotinylated cross-linker for structural proteomics. Mol Cell Proteom 10:M110 001420","journal-title":"Mol Cell Proteom"},{"key":"222_CR30","doi-asserted-by":"publisher","first-page":"7500","DOI":"10.1021\/acs.chemrev.1c00786","volume":"122","author":"L Piersimoni","year":"2022","unstructured":"Piersimoni L, Kastritis PL, Arlt C, Sinz A (2022) Cross-linking mass spectrometry for investigating protein conformations and protein-protein interactions\u2014a method for all seasons. Chem Rev 122:7500\u20137531","journal-title":"Chem Rev"},{"key":"222_CR31","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1021\/acs.jproteome.9b00541","volume":"19","author":"PSJ Ryl","year":"2020","unstructured":"Ryl PSJ, Bohlke-Schneider M, Lenz S, Fischer L, Budzinski L, Stuiver M, Mendes MML, Sinn L, O\u2019Reilly FJ, Rappsilber J (2020) In situ structural restraints from cross-linking mass spectrometry in human mitochondria. J Proteome Res 19:327\u2013336","journal-title":"J Proteome Res"},{"key":"222_CR32","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1021\/jasms.9b00085","volume":"31","author":"B Steigenberger","year":"2020","unstructured":"Steigenberger B, Albanese P, Heck AJR, Scheltema RA (2020) To cleave or not to cleave in XL-MS?. J Am Soc Mass Spectrom 31:196\u2013206","journal-title":"J Am Soc Mass Spectrom"},{"key":"222_CR33","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1021\/acscentsci.9b00416","volume":"5","author":"B Steigenberger","year":"2019","unstructured":"Steigenberger B, Pieters RJ, Heck AJR, Scheltema RA (2019a) PhoX: an IMAC-enrichable cross-linking reagent. ACS Cent Sci 5:1514\u20131522","journal-title":"ACS Cent Sci"},{"key":"222_CR34","doi-asserted-by":"publisher","first-page":"116184","DOI":"10.1016\/j.ijms.2019.116184","volume":"444","author":"B Steigenberger","year":"2019","unstructured":"Steigenberger B, Schiller HB, Pieters RJ, Scheltema RA (2019b) Finding and using diagnostic ions in collision induced crosslinked peptide fragmentation spectra. Int J Mass Spectrom 444:116184","journal-title":"Int J Mass Spectrom"},{"key":"222_CR35","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1021\/acs.jproteome.8b00947","volume":"18","author":"CE Stieger","year":"2019","unstructured":"Stieger CE, Doppler P, Mechtler K (2019) Optimized fragmentation improves the identification of peptides cross-linked by MS-cleavable reagents. J Proteome Res 18:1363\u20131370","journal-title":"J Proteome Res"},{"key":"222_CR36","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12509","volume":"5","author":"D Tan","year":"2016","unstructured":"Tan D, Li Q, Zhang MJ, Liu C, Ma C, Zhang P, Ding YH, Fan SB, Tao L, Yang B et al (2016) Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states. eLife 5:e12509","journal-title":"eLife"},{"key":"222_CR37","doi-asserted-by":"publisher","first-page":"239","DOI":"10.52601\/bpr.2022.220014","volume":"8","author":"JH Wang","year":"2022","unstructured":"Wang JH, Gong Z, Dong X, Liu SQ, Tang YL, Lei X, Tang C, Dong MQ (2022a) Fast cross-linking by DOPA2 promotes the capturing of a stereospecific protein complex over nonspecific encounter complexes. Biophys Rep 8:239\u2013252","journal-title":"Biophys Rep"},{"key":"222_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28879-4","volume":"13","author":"JH Wang","year":"2022","unstructured":"Wang JH, Tang YL, Gong Z, Jain R, Xiao F, Zhou Y, Tan D, Li Q, Huang N, Liu SQ et al (2022b) Characterization of protein unfolding by fast cross-linking mass spectrometry using di-ortho-phthalaldehyde cross-linkers. Nat Commun 13:1468","journal-title":"Nat Commun"},{"key":"222_CR39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2023360118","volume":"118","author":"A Wheat","year":"2021","unstructured":"Wheat A, Yu C, Wang X, Burke AM, Chemmama IE, Kaake RM, Baker P, Rychnovsky SD, Yang J, Huang L (2021) Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry. Proc Natl Acad Sci USA 118:e2023360118","journal-title":"Proc Natl Acad Sci USA"},{"key":"222_CR40","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nature17942","volume":"534","author":"S Wu","year":"2016","unstructured":"Wu S, Tutuncuoglu B, Yan K, Brown H, Zhang Y, Tan D, Gamalinda M, Yuan Y, Li Z, Jakovljevic J et al (2016) Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes. Nature 534:133\u2013137","journal-title":"Nature"},{"key":"222_CR41","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/nmeth.2099","volume":"9","author":"B Yang","year":"2012","unstructured":"Yang B, Wu YJ, Zhu M, Fan SB, Lin J, Zhang K, Li S, Chi H, Li YX, Chen HF et al (2012) Identification of cross-linked peptides from complex samples. Nat Methods 9:904\u2013906","journal-title":"Nat Methods"},{"key":"222_CR42","doi-asserted-by":"publisher","first-page":"5802","DOI":"10.1073\/pnas.090099097","volume":"97","author":"MM Young","year":"2000","unstructured":"Young MM, Tang N, Hempel JC, Oshiro CM, Taylor EW, Kuntz ID, Gibson BW, Dollinger G (2000) High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry. Proc Natl Acad Sci USA 97:5802\u20135806","journal-title":"Proc Natl Acad Sci USA"},{"key":"222_CR43","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1021\/acs.analchem.7b04431","volume":"90","author":"C Yu","year":"2018","unstructured":"Yu C, Huang L (2018) Cross-linking mass spectrometry: an emerging technology for interactomics and structural biology. Anal Chem 90:144\u2013165","journal-title":"Anal Chem"},{"key":"222_CR44","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1074\/mcp.TIR119.001847","volume":"19","author":"K Yugandhar","year":"2020","unstructured":"Yugandhar K, Wang TY, Leung AK, Lanz MC, Motorykin I, Liang J, Shayhidin EE, Smolka MB, Zhang S, Yu H (2020) MaXLinker: proteome-wide cross-link identifications with high specificity and sensitivity. Mol Cell Proteom 19:554\u2013568","journal-title":"Mol Cell Proteom"},{"key":"222_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52558-1","volume":"15","author":"L Zhao","year":"2024","unstructured":"Zhao L, An Y, Zhao N, Gao H, Zhang W, Gong Z, Liu X, Zhao B, Liang Z, Tang C et al (2024) Spatially resolved profiling of protein conformation and interactions by biocompatible chemical cross-linking in living cells. Nat Commun 15:8331","journal-title":"Nat Commun"},{"key":"222_CR46","doi-asserted-by":"publisher","first-page":"3649","DOI":"10.1021\/jacsau.5c00709","volume":"5","author":"Y Zhou","year":"2025","unstructured":"Zhou Y, Zhang B, Zhong B, Sun M, Zhang X, Zhang Y, Zhang L, Zhao Q, Gong Z, Liu M (2025) Dissecting in vivo cross-linker performance: insights into structural dynamics and molecular rigidity. JACS Au 5:3649\u20133659","journal-title":"JACS Au"},{"key":"222_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47569-x","volume":"15","author":"Y Zhu","year":"2024","unstructured":"Zhu Y, Akkaya KC, Ruta J, Yokoyama N, Wang C, Ruwolt M, Lima DB, Lehmann M, Liu F (2024) Cross-link assisted spatial proteomics to map sub-organelle proteomes and membrane protein topologies. Nat Commun 15:3290","journal-title":"Nat Commun"}],"container-title":["Molecular Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44320-026-00222-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1038\/s44320-026-00222-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1038\/s44320-026-00222-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:32:57Z","timestamp":1788330777000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1038\/s44320-026-00222-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,2]]}},"alternative-id":["222"],"URL":"https:\/\/doi.org\/10.1038\/s44320-026-00222-9","relation":{},"ISSN":["1744-4292"],"issn-type":[{"value":"1744-4292","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]},"assertion":[{"value":"4 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure and competing interests statement"}}]}}