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Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations characterized by distinct interactomes\u2014namely, protein assemblies\u2014under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation\u2019s influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly, and disease.<\/jats:p>","DOI":"10.3390\/biom14030282","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T03:35:48Z","timestamp":1709004948000},"page":"282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5612-6241","authenticated-orcid":false,"given":"Chiranjeevi","family":"Pasala","sequence":"first","affiliation":[{"name":"Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7281-9224","authenticated-orcid":false,"given":"Sahil","family":"Sharma","sequence":"additional","affiliation":[{"name":"Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanaya","family":"Roychowdhury","sequence":"additional","affiliation":[{"name":"Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7705-7457","authenticated-orcid":false,"given":"Elisabetta","family":"Moroni","sequence":"additional","affiliation":[{"name":"The Institute of Chemical Sciences and Technologies (SCITEC), Italian National Research Council (CNR), 20131 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Colombo","sequence":"additional","affiliation":[{"name":"The Institute of Chemical Sciences and Technologies (SCITEC), Italian National Research Council (CNR), 20131 Milano, Italy"},{"name":"Department of Chemistry, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Chiosis","sequence":"additional","affiliation":[{"name":"Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"},{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nrm3383","article-title":"Vertebrate protein glycosylation: Diversity, synthesis and function","volume":"13","author":"Moremen","year":"2012","journal-title":"Nat. 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