{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:15:31Z","timestamp":1785417331203,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,14]]},"group-title":"Biophysics","reference-count":44,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"award":["R01AI166050"],"award-info":[{"award-number":["R01AI166050"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Glycosylation is a pivotal post-translational modification that influences protein folding, stability, and interactions, with direct implications for muscular dystrophy pathogenesis and emerging gene therapies. Sarcoglycans (SGs),\n                  <jats:italic>\u03b2<\/jats:italic>\n                  -,\n                  <jats:italic>\u03b4<\/jats:italic>\n                  -,\n                  <jats:italic>\u03b3<\/jats:italic>\n                  -, and\n                  <jats:italic>\u03b1<\/jats:italic>\n                  - subunits of the dystrophin\u2013glycoprotein complex (DGC), contain essential N-linked glycosylation sites, and mutations that disrupt glycan attachment, destabilize the complex and cause limb-girdle muscular dystrophy. Yet, the structural consequences of SG glycosylation remain poorly defined due to the absence of experimental sarcoglycan complex structures. Here, we use homology modeling, AlphaFold predictions, and allatom molecular dynamics simulations to probe how N-linked glycans reshape the conformational ensembles of\n                  <jats:italic>\u03b2<\/jats:italic>\n                  -,\n                  <jats:italic>\u03b4<\/jats:italic>\n                  -, and\n                  <jats:italic>\u03b3<\/jats:italic>\n                  -SG monomers and the\n                  <jats:italic>\u03b2<\/jats:italic>\n                  \u2013\n                  <jats:italic>\u03b4<\/jats:italic>\n                  \u2013\n                  <jats:italic>\u03b3<\/jats:italic>\n                  heterotrimer core. We find that glycosylation increases flexibility and conformational heterogeneity in isolated monomers but reinforces a compact, stabilized architecture in the heterotrimer. Contact map and clustering analyses show that glycans redistribute local residue interactions while preserving global trimer organization, suggesting a context-dependent role in destabilizing monomers yet reinforcing complex stability. These findings provide the first atomistic insight into how glycosylation primes sarcoglycans for assembly and may explain why mutations at glycosylation sites disrupt complex integrity and drive muscular dystrophy phenotypes.\n                <\/jats:p>","DOI":"10.64898\/2026.01.13.699269","type":"posted-content","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T21:20:11Z","timestamp":1768425611000},"source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Glycosylation on the Conformational Ensembles of\n                  <i>\u03b2<\/i>\n                  -,\n                  <i>\u03b4<\/i>\n                  -, and\n                  <i>\u03b3<\/i>\n                  Sarcoglycans"],"prefix":"10.64898","author":[{"given":"Elham","family":"Fazelpour","sequence":"first","affiliation":[{"name":"Department of Chemistry, Oklahoma State University, Stillwater, OK 74078"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel A.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Oklahoma State University, Stillwater, OK 74078"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-4388","authenticated-orcid":false,"given":"Martin","family":"McCullagh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Oklahoma State University, Stillwater, OK 74078"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020605570964000_2026.01.13.699269v1.1","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1093\/oxfordjournals.jbchem.a123276","article-title":"Glycoprotein complex anchoring dystrophin to sarcolemma","volume":"108","year":"1990","journal-title":"The Journal of Biochemistry"},{"key":"2026020605570964000_2026.01.13.699269v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90035-W"},{"key":"2026020605570964000_2026.01.13.699269v1.3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.52.34667"},{"key":"2026020605570964000_2026.01.13.699269v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10566"},{"key":"2026020605570964000_2026.01.13.699269v1.5","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.143.7.2033"},{"key":"2026020605570964000_2026.01.13.699269v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.01.024"},{"key":"2026020605570964000_2026.01.13.699269v1.7","unstructured":"U.S. Food and Drug Administration FDA Requests Sarepta Therapeutics Suspend Distribution of Elevidys and Places Clinical Trials on Hold Following Three Deaths. 2025; https:\/\/t.co\/lQAwI5WCOw, 2025-07-18."},{"key":"2026020605570964000_2026.01.13.699269v1.8","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/s41586-024-08324-w","article-title":"Native DGC structure rationalizes muscular dystrophy-causing mutations","volume":"637","year":"2025","journal-title":"Nature"},{"key":"2026020605570964000_2026.01.13.699269v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08310-2"},{"key":"2026020605570964000_2026.01.13.699269v1.10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00521.2015"},{"key":"2026020605570964000_2026.01.13.699269v1.11","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky092"},{"key":"2026020605570964000_2026.01.13.699269v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-021-03819-2"},{"key":"2026020605570964000_2026.01.13.699269v1.13","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAD1011"},{"key":"2026020605570964000_2026.01.13.699269v1.14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"2026020605570964000_2026.01.13.699269v1.15","doi-asserted-by":"crossref","first-page":"e1008667","DOI":"10.1371\/journal.pcbi.1008667","article-title":"ProMod3\u2014A versatile homology modelling toolbox","volume":"17","year":"2021","journal-title":"PLoS computational biology"},{"key":"2026020605570964000_2026.01.13.699269v1.16","doi-asserted-by":"crossref","first-page":"40904","DOI":"10.1021\/acsomega.3c06135","article-title":"In Vitro Glycosylation of the Membrane Protein \u03b3-Sarcoglycan in Nanodiscs","volume":"8","year":"2023","journal-title":"ACS omega"},{"key":"2026020605570964000_2026.01.13.699269v1.17","unstructured":"Case, D. 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