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This behavior is hypothesized to originate from exposed interior hydrophobic residues upon denaturation with nearly complete unfolding upon ejection of the protein. In this work, we demonstrate that natively unstructured, strongly hydrophilic proline\/alanine\/serine (PAS) sequences and even folded proteins derivatized with PAS tails can also ionize at least partly through CEM. To determine the mechanistic origin of hydrophilic CEM, PAS tails of different lengths were analyzed and conjugated to bovine serum albumin. The solution-phase sizes of the species correlate well with the size of droplets that efficiently emit small ions through ion evaporation, thus offering a mechanism for CEM in the absence of hydrophobicity. The charge-state distributions and folding state of these structured\/unstructured hybrids upon ionization were monitored by IMS-MS, showing that CEM ionization can induce partial as well as complete unfolding of folded proteins. This results in CEM-like charge acquisition and signal enhancement to an extent that is dependent on the relative size of the natively unfolded region.<\/jats:p>","DOI":"10.1021\/jasms.6c00080","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:20:49Z","timestamp":1788351649000},"page":"2301-2309","source":"Crossref","is-referenced-by-count":0,"title":["Addition of Unstructured\nProline\/Alanine\/Serine (PAS)\nTails to Folded Proteins Induces Chain Ejection Model Ionization in\nNative ESI-MS"],"prefix":"10.1021","volume":"37","author":[{"given":"Alex","family":"Listigovers","sequence":"first","affiliation":[{"name":"York University , , , ,","place":["Toronto, Ontario, Canada, M3J 1P3"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Andrew","family":"James","sequence":"additional","affiliation":[{"name":"Sanofi Vaccines Canada Ltd , , ,","place":["Toronto, Ontario, Canada, M2R 3T4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Friedrich","sequence":"additional","affiliation":[{"name":"XL-Protein GmbH , Lise-Meitner-Str. 30 , ,","place":["Freising, Germany, 85354"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Walser","sequence":"additional","affiliation":[{"name":"XL-Protein GmbH , Lise-Meitner-Str. 30 , ,","place":["Freising, Germany, 85354"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-498X","authenticated-orcid":true,"given":"Arne","family":"Skerra","sequence":"additional","affiliation":[{"name":"Technical University of Munich , , ,","place":["Freising, Germany, 85354"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7012-6085","authenticated-orcid":true,"given":"Derek J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"York University , , , ,","place":["Toronto, Ontario, Canada, M3J 1P3"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"issue":"16","key":"2026100710064276400_cit1","doi-asserted-by":"publisher","first-page":"5370","DOI":"10.1021\/ac050511+","article-title":"Estimates of Protein\nSurface Areas in Solution by Electrospray\nIonization Mass Spectrometry","volume":"77","author":"Kaltashov","year":"2005","journal-title":"Anal. 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