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These fungi are distinguished by a distinctive cell wall architecture further reinforced by two virulence\u2010associated layers, melanin and capsule, rendering them insensitive to antifungal agents targeting the cell wall, such as echinocandins. The molecular interplay between these three biomolecular layers remains poorly understood. Here, we employ solid\u2010state NMR spectroscopy to examine intact cells of both wild\u2010type and capsule\u2010deficient strains of\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    , along with melanized cells. High\u2010resolution\n                    <jats:sup>13<\/jats:sup>\n                    C and\n                    <jats:sup>1<\/jats:sup>\n                    H data revealed five distinct structural forms of \u03b1\u20101,3\u2010glucans that play versatile roles in forming the rigid cell wall scaffold by interacting with chitin microfibrils and chitosan, and in stabilizing the mobile matrix by associating with \u03b2\u20101,6\u2010glucan and a small fraction of \u03b2\u20101,3\u2010glucan. Two primary forms of \u03b1\u20101,3\u2010glucans were distributed throughout the wall, capable of hosting melanin deposition in the inner domain and capsule attachment on the cell surface. These findings offer a paradigm shift in understanding the cryptococcal cell wall and its interaction with two key virulence factors on opposite sides, raising critical biochemical questions that could inform the development of more effective antifungal treatments for cryptococcosis.\n                  <\/jats:p>","DOI":"10.1002\/anie.202510409","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T10:34:49Z","timestamp":1751970889000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Polymorphic \u03b1\u2010Glucans as Structural Scaffolds in\n                    <i>Cryptococcus<\/i>\n                    Cell Walls for Chitin, Capsule, and Melanin: Insights From\n                    <sup>13<\/sup>\n                    C and\n                    <sup>1<\/sup>\n                    H Solid\u2010State NMR"],"prefix":"10.1002","volume":"64","author":[{"given":"Ankur","family":"Ankur","sequence":"first","affiliation":[{"name":"Department of Chemistry Michigan State University  East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayasubba Reddy","family":"Yarava","sequence":"additional","affiliation":[{"name":"Department of Chemistry Michigan State University  East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Gautam","sequence":"additional","affiliation":[{"name":"Department of Chemistry Michigan State University  East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith J.","family":"Scott","sequence":"additional","affiliation":[{"name":"National High Magnetic Field Laboratory Florida State University  Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Mentink\u2010Vigier","sequence":"additional","affiliation":[{"name":"National High Magnetic Field Laboratory Florida State University  Tallahassee FL USA"},{"name":"Department of Chemistry and Biochemistry Florida State University  Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Chrissian","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry City College of New York  New York NY USA"},{"name":"CUNY Institute for Macromolecular Assemblies The City University of New York  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Chemistry Michigan State University  East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dibakar","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Chemistry Michigan State University  East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth E.","family":"Stark","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry City College of New York  New York NY USA"},{"name":"CUNY Institute for Macromolecular Assemblies The City University of New York  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara L.","family":"Doering","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology Washington University in St. Louis School of Medicine  St. Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Microbiology, Immunology &amp; 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