{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:27:02Z","timestamp":1781778422895,"version":"3.54.5"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,10,18]]},"abstract":"<jats:p>\n                    \u03b1-dystroglycan is a highly\n                    <jats:italic>O<\/jats:italic>\n                    -glycosylated extracellular matrix receptor that is required for anchoring of the basement membrane to the cell surface and for the entry of Old World arenaviruses into cells. Like-acetylglucosaminyltransferase (LARGE) is a key molecule that binds to the N-terminal domain of \u03b1-dystroglycan and attaches ligand-binding moieties to phosphorylated\n                    <jats:italic>O<\/jats:italic>\n                    -mannose on \u03b1-dystroglycan. Here we show that the LARGE modification required for laminin- and virus-binding occurs on specific Thr residues located at the extreme N terminus of the mucin-like domain of \u03b1-dystroglycan. Deletion and mutation analyses demonstrate that the ligand-binding activity of \u03b1-dystroglycan is conferred primarily by LARGE modification at Thr-317 and -319, within the highly conserved first 18 amino acids of the mucin-like domain. The importance of these paired residues in laminin-binding and clustering activity on myoblasts and in arenavirus cell entry is confirmed by mutational analysis with full-length dystroglycan. We further demonstrate that a sequence of five amino acids, Thr\n                    <jats:sup>317<\/jats:sup>\n                    ProThr\n                    <jats:sup>319<\/jats:sup>\n                    ProVal, contains phosphorylated\n                    <jats:italic>O<\/jats:italic>\n                    -glycosylation and, when modified by LARGE is sufficient for laminin-binding. Because the N-terminal region adjacent to the paired Thr residues is removed during posttranslational maturation of dystroglycan, our results demonstrate that the ligand-binding activity resides at the extreme N terminus of mature \u03b1-dystroglycan and is crucial for \u03b1-dystroglycan to coordinate the assembly of extracellular matrix proteins and to bind arenaviruses on the cell surface.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1114836108","type":"journal-article","created":{"date-parts":[[2011,10,11]],"date-time":"2011-10-11T01:31:58Z","timestamp":1318296718000},"page":"17426-17431","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":111,"title":["Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317\/319 is required for laminin binding and arenavirus infection"],"prefix":"10.1073","volume":"108","author":[{"given":"Yuji","family":"Hara","sequence":"first","affiliation":[{"name":"The Howard Hughes Medical Institute, Departments of"},{"name":"Molecular Physiology and Biophysics,"},{"name":"Neurology, and"},{"name":"Internal Medicine, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoi","family":"Kanagawa","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, Departments of"},{"name":"Molecular Physiology and Biophysics,"},{"name":"Neurology, and"},{"name":"Internal Medicine, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kunz","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University Hospital Center and"},{"name":"University of Lausanne, Lausanne CH-1011, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Yoshida-Moriguchi","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, Departments of"},{"name":"Molecular Physiology and Biophysics,"},{"name":"Neurology, and"},{"name":"Internal Medicine, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob S.","family":"Satz","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, Departments of"},{"name":"Molecular Physiology and Biophysics,"},{"name":"Neurology, and"},{"name":"Internal Medicine, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M.","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, Departments of"},{"name":"Molecular Physiology and Biophysics,"},{"name":"Neurology, and"},{"name":"Internal Medicine, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, Departments of"},{"name":"Molecular Physiology and Biophysics,"},{"name":"Neurology, and"},{"name":"Internal Medicine, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Burden","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, NY 10016; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B. A.","family":"Oldstone","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P.","family":"Campbell","sequence":"additional","affiliation":[{"name":"The Howard Hughes Medical Institute, Departments of"},{"name":"Molecular Physiology and Biophysics,"},{"name":"Neurology, and"},{"name":"Internal Medicine, The Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,10,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R200031200"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906545106"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02814"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00837"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.122.4.809"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2011.02.001"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2079"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.10.5140-5146.2002"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.11.023"},{"key":"e_1_3_3_10_2","first-page":"1","article-title":"Lymphocytic choriomeningitis virus and immunology","volume":"263","author":"Zinkernagel RM","year":"2002","unstructured":"RM Zinkernagel, Lymphocytic choriomeningitis virus and immunology. Curr Top Microbiol Immunol 263, 1\u20135 (2002).","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200104103"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.22.14282-14296.2005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2076"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/88865"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.07.059"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.003"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1006939"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1180512"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi062"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1059"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81708-0"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.1.46-57.2004"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06243.x"},{"key":"e_1_3_3_24_2","first-page":"375","volume-title":"Essentials of Glycobiology","author":"Varki A","year":"2009","unstructured":"A Varki, ME Etzler, RD Cummings, JD Esko Essentials of Glycobiology, eds A Varki, et al. (Cold Spring Harbor, New York), pp. 375\u2013386 (2009)."},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050375"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610657200"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1114836108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:47:14Z","timestamp":1649796434000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1114836108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,10]]},"references-count":26,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2011,10,18]]}},"alternative-id":["10.1073\/pnas.1114836108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1114836108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,10]]},"assertion":[{"value":"2011-10-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}