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These structures can be comprised of many biomolecules, but especially lipids, proteins, and nucleic acids. Techniques are limited to quantify or discover new subcellular structures. We explored whether a proteomics approach using chemical crosslinking followed by size\u2010exclusion chromatography and mass spectrometry (SEC\u2010MS) of whole cell lysates can address this challenge. Formaldehyde crosslinking was used to preserve the weak molecular interactions responsible for many protein and nucleic acid assemblies. In this study, we perform the first formaldehyde crosslinking\u2010assisted SEC\u2010MS in a bacterial system. We demonstrate that when expressed ectopically in\n                    <jats:italic>E. coli<\/jats:italic>\n                    , large structures of a known assembly protein, FUS, can be detected through SEC\u2010MS. We then show that\n                    <jats:italic>E. coli<\/jats:italic>\n                    proteins are enriched in particles of large or medium size due to formaldehyde crosslinking, which is the first analysis by formaldehyde and SEC\u2010MS for a bacterial system. Last, analysis identified previously characterized\n                    <jats:italic>E. coli<\/jats:italic>\n                    protein assemblies and condensates, as well as potentially novel associations of prokaryote metabolism with large subcellular bodies. We propose this unbiased method can be used to stimulate or supplement targeted methods for discovery of new cellular bodies in a wide range of cell types.\n                  <\/jats:p>","DOI":"10.1002\/pmic.70105","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T06:36:27Z","timestamp":1769063787000},"page":"27-36","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identifying Subcellular Structure Components in\n                    <i>Escherichia Coli<\/i>\n                    by Crosslinking and SEC\u2010MS"],"prefix":"10.1002","volume":"26","author":[{"given":"Rachel A.","family":"Victor","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Lipinski","sequence":"additional","affiliation":[{"name":"Department of 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