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Sci.","IJMS"],"abstract":"<jats:p>Studying protein structure dynamics is key to understanding protein function modulation. Alternative protein conformations are well discriminated from each other by nanoESI mass spectrometry and ion mobility measurements. Experimentally determined collisional cross-sections were compared to calculated collisional cross-sections of fifteen peptides, single-domain proteins, and protein complexes. The multi-domain proteins investigated here, four immunoglobulin G (IgG) antibodies and protein G, are present as compacted\/folded \u201cnative\u201d conformations in neutral buffered solutions, and they are identified by molecular ions with narrow charge-state distributions, relatively few charges, and small collisional cross-sections. Simultaneously present extended\/folded but nevertheless \u201cnative\u201d conformations produced additional ions with higher charge states, different charge-state distributions, and larger collisional cross-sections. Computed collisional cross-sections from compacted \u201co-shape\u201d and extended \u201cl-shape\u201d protein G three-dimensional (3D) structures match experimental data, indicating equilibrium, and suggest a dynamic \u201co2l\u201d flip process. Likewise, \u201cm-shape\u201d (compacted) and \u201cY-shape\u201d (extended) IgGs are regarded as two supposedly reversibly adopted antibody conformations which may interchange by an \u201cm2Y\u201d flip. Adopting an m-shape would prevent an antibody-based initiation of humoral and cellular immune system responses, such as opsonophagocytosis, prior to antigen contact, which stands in line with the rearrangement hypothesis.<\/jats:p>","DOI":"10.3390\/ijms27177662","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:54:42Z","timestamp":1787763282000},"page":"7662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Four IgG Antibodies and Protein G Are Shapeshifters"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-482X","authenticated-orcid":false,"given":"Michael O.","family":"Glocker","sequence":"first","affiliation":[{"name":"Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Schillingallee 69, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5550-4618","authenticated-orcid":false,"given":"Manuela","family":"Ru\u00df","sequence":"additional","affiliation":[{"name":"Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Schillingallee 69, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3475-1799","authenticated-orcid":false,"given":"Cornelia","family":"Koy","sequence":"additional","affiliation":[{"name":"Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Schillingallee 69, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3331-7584","authenticated-orcid":false,"given":"Michael","family":"Kreutzer","sequence":"additional","affiliation":[{"name":"Proteome Center Rostock, Medical Faculty and Natural Science Faculty, University of Rostock, Schillingallee 69, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7181-9369","authenticated-orcid":false,"given":"Fiona T. 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