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Here, we use a combination of ion mobility-mass spectrometry (IM-MS) and molecular dynamics (MD) simulations at elevated temperatures for enhanced sampling to explore the conformational landscape of COR15A. The IM-MS data display charge states from +5 to +12, and collision cross section (CCS) distributions indicative of two dominant coexisting conformational families centered on approximately 1200 and 1800 \u00c52, with subconformers evident. The structures sampled with MD are histogrammed, which provides a pseudo-CCS distribution (pCCS) highly similar to experimental IM-MS data, allowing us to compare with small-angle X-ray scattering-derived structures of COR15A in functional conditions. This approach gives compelling evidence that the experimental gas-phase data correspond to natively accessible states. In contrast to commonly used biophysical approaches, IM-MS permits simultaneous observation of disordered forms as well as conformers populated upon dehydration, allowing insights into dehydration-responsive LEA proteins.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c02199","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:09:35Z","timestamp":1785848975000},"page":"7809-7818","source":"Crossref","is-referenced-by-count":0,"title":["Mapping the Conformational Landscape of the Cold-Regulated\nIntrinsically Disordered Protein COR15A"],"prefix":"10.1021","volume":"130","author":[{"given":"Dale","family":"Stuchfield","sequence":"first","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, U.K., M13 9PL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8104-0612","authenticated-orcid":true,"given":"Ana","family":"Bath Ale\u0301n","sequence":"additional","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, U.K., M13 9PL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Venables","sequence":"additional","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, U.K., M13 9PL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6480-0993","authenticated-orcid":true,"given":"Anja","family":"Thalhammer","sequence":"additional","affiliation":[{"name":"Universita\u0308t Potsdam , , Am Neuen Palais 10 , ,","place":["Potsdam, Germany, 14476"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7720-586X","authenticated-orcid":true,"given":"Perdita E.","family":"Barran","sequence":"additional","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, U.K., M13 9PL"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5306-3644","authenticated-orcid":true,"given":"Charles","family":"Eldrid","sequence":"additional","affiliation":[{"name":"University of Manchester , , Oxford Road , ,","place":["Manchester, U.K., M13 9PL"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026080608123850700_cit1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58656-y","article-title":"Life on\nthe Dry Side: A Roadmap to Understanding Desiccation Tolerance and\nAccelerating Translational Applications","volume":"16","author":"Marks","year":"2025","journal-title":"Nat.\nCommun."},{"key":"2026080608123850700_cit2","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.crbiot.2021.07.005","article-title":"Dehydrin in the Past Four Decades:\nFrom Chaperones to Transcription Co-Regulators in Regulating Abiotic\nStress Response","volume":"3","author":"Tiwari","year":"2021","journal-title":"Curr. Res. Biotechnol."},{"issue":"19","key":"2026080608123850700_cit3","doi-asserted-by":"publisher","first-page":"6525","DOI":"10.1093\/jxb\/erac293","article-title":"LEAfing through\nLiterature: Late Embryogenesis Abundant Proteins Coming of Age\u2500Achievements\nand Perspectives","volume":"73","author":"Herna\u0301ndez-Sa\u0301nchez","year":"2022","journal-title":"J. Exp. Bot."},{"issue":"4","key":"2026080608123850700_cit4","doi-asserted-by":"publisher","first-page":"536","DOI":"10.2478\/s11658-006-0044-0","article-title":"Plant Dehydrins\u2500Tissue\nLocation, Structure and Function","volume":"11","author":"Rorat","year":"2006","journal-title":"Cell. Mol.\nBiol. Lett."},{"issue":"17","key":"2026080608123850700_cit5","doi-asserted-by":"publisher","first-page":"5551","DOI":"10.1007\/s00253-022-12080-0","article-title":"Evaluation of a Bacterial Group 1 LEA Protein as an\nEnzyme Protectant from Stress-Induced Inactivation","volume":"106","author":"Raga-Carbajal","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"issue":"1","key":"2026080608123850700_cit6","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/j.1574-6968.2004.tb09624.x","article-title":"Isolation\nof a New Member of Group\n3 Late Embryogenesis Abundant Protein Gene from a Halotorelant Green\nAlga by a Functional Expression Screening with Cyanobacterial Cells","volume":"236","author":"Tanaka","year":"2004","journal-title":"FEMS Microbiol. 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Biol."},{"issue":"1","key":"2026080608123850700_cit29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007537","article-title":"Inhibition of the Staphylococcus\nAureus C-Di-AMP Cyclase DacA by Direct Interaction with the Phosphoglucosamine\nMutase GlmM","volume":"15","author":"Tosi","year":"2019","journal-title":"PLoS Pathog."},{"key":"2026080608123850700_cit30","doi-asserted-by":"publisher","first-page":"8021","DOI":"10.1021\/jacs.3c00291","article-title":"Uncovering the Role\nof N -Glycan Occupancy on the Cooperative Assembly\nof Spike and Angiotensin Converting Enzyme 2 Complexes: Insights from\nGlycoengineering and Native Mass Spectrometry","volume":"145","author":"El-Baba","year":"2023","journal-title":"J. Am. Chem. Soc."},{"issue":"6054","key":"2026080608123850700_cit31","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1126\/science.1210148","article-title":"Mass Spectrometry of Intact V-Type\nATPases Reveals Bound Lipids and the Effects of Nucleotide Binding","volume":"334","author":"Zhou","year":"2011","journal-title":"Science"},{"issue":"8","key":"2026080608123850700_cit32","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1002\/pro.2706","article-title":"An Integrative\nApproach Combining Ion Mobility Mass Spectrometry, X-Ray Crystallography,\nand Nuclear Magnetic Resonance Spectroscopy to Study the Conformational\nDynamics of \u03911-Antitrypsin upon Ligand Binding","volume":"24","author":"Nyon","year":"2015","journal-title":"Protein Sci."},{"issue":"17","key":"2026080608123850700_cit33","doi-asserted-by":"publisher","first-page":"4037","DOI":"10.1007\/s00216-020-02649-x","article-title":"Screening\nof Protein-Ligand Interactions under Crude Conditions by Native Mass\nSpectrometry","volume":"412","author":"Takano","year":"2020","journal-title":"Anal Bioanal Chem."},{"issue":"22","key":"2026080608123850700_cit34","doi-asserted-by":"publisher","first-page":"11509","DOI":"10.1021\/acs.analchem.5b03291","article-title":"Collision Induced Unfolding of Intact\nAntibodies: Rapid Characterization of Disulfide Bonding Patterns,\nGlycosylation, and Structures","volume":"87","author":"Tian","year":"2015","journal-title":"Anal. 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Soc."},{"key":"2026080608123850700_cit49","doi-asserted-by":"publisher","first-page":"12541","DOI":"10.1021\/jacs.3c00756","article-title":"Ion Mobility Mass Spectrometry Unveils\nGlobal Protein\nConformations in Response to Conditions That Promote and Reverse Liquid\u2013Liquid\nPhase Separation","volume":"145","author":"Robb","year":"2023","journal-title":"J. Am. Chem. Soc."},{"issue":"3\u20134","key":"2026080608123850700_cit50","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.202000011","article-title":"Emerging Role\nof Mass Spectrometry-Based Structural Proteomics in Elucidating Intrinsic\nDisorder in Proteins","volume":"21","author":"Mitra","year":"2021","journal-title":"PROTEOMICS"},{"issue":"34","key":"2026080608123850700_cit51","doi-asserted-by":"publisher","first-page":"18727","DOI":"10.1039\/C9CP01768B","article-title":"Conformational Selection of the Intrinsically\nDisordered Plant Stress Protein COR15A in Response to Solution Osmolarity\n\u2013 an X-Ray and Light Scattering Study","volume":"21","author":"Shou","year":"2019","journal-title":"Phys. Chem. Chem. Phys."},{"issue":"22","key":"2026080608123850700_cit52","doi-asserted-by":"publisher","first-page":"9557","DOI":"10.1021\/ac1022953","article-title":"Collision Cross\nSections of Proteins and Their Complexes:\nA Calibration Framework and Database for Gas-Phase Structural Biology","volume":"82","author":"Bush","year":"2010","journal-title":"Anal. Chem."},{"issue":"3","key":"2026080608123850700_cit53","doi-asserted-by":"publisher","DOI":"10.3390\/biom9030084","article-title":"Conserved Glycines Control Disorder\nand Function in the Cold-Regulated Protein, COR15A","volume":"9","author":"Sowemimo","year":"2019","journal-title":"Biomolecules"},{"issue":"12","key":"2026080608123850700_cit54","doi-asserted-by":"publisher","first-page":"7554","DOI":"10.1021\/acs.analchem.8b05641","article-title":"Gas Phase Stability of Protein Ions\nin a Cyclic Ion Mobility Spectrometry Traveling Wave Device","volume":"91","author":"Eldrid","year":"2019","journal-title":"Anal. 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