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In this study we combined cross-link\u2013derived spatial constraints with homology modeling to produce the first experimentally verified medium-resolution structures of wild-type spectrin closed dimers and tetramers. These structures coupled with the closed dimer structure of a very common spectrin mutation associated with hereditary hemolytic anemia provide mechanistic insights into how some mutations located large distances from the spectrin tetramerization site can destabilize red cell membranes.<\/jats:p>","DOI":"10.1073\/pnas.1317620111","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T22:42:30Z","timestamp":1390430550000},"page":"1801-1806","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["Probing large conformational rearrangements in wild-type and mutant spectrin using structural mass spectrometry"],"prefix":"10.1073","volume":"111","author":[{"given":"Sira","family":"Sriswasdi","sequence":"first","affiliation":[{"name":"Center for Systems and Computational Biology, and Molecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104;"},{"name":"Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Harper","sequence":"additional","affiliation":[{"name":"Center for Systems and Computational Biology, and Molecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yao","family":"Tang","sequence":"additional","affiliation":[{"name":"Center for Systems and Computational Biology, and Molecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick G.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Speicher","sequence":"additional","affiliation":[{"name":"Center for Systems and Computational Biology, and Molecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104;"},{"name":"Genomics and Computational Biology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,1,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090099097"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.401"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120559109"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2012.03.007"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1221483"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201200305"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R000001-MCP201"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mas.20082"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00721-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.54.070185.001421"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.09.110193.000331"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00159a030"},{"key":"e_1_3_3_13_2","first-page":"21","article-title":"Mutations involving the spectrin heterodimer contact site: Clinical expression and alterations in specific function","volume":"30","author":"Delaunay J","year":"1993","unstructured":"J Delaunay, D Dhermy, Mutations involving the spectrin heterodimer contact site: Clinical expression and alterations in specific function. Semin Hematol 30, 21\u201333 (1993).","journal-title":"Semin Hematol"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2004.01.003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1172\/JCI115669","article-title":"A common type of the spectrin alpha I 46-50a-kD peptide abnormality in hereditary elliptocytosis and pyropoikilocytosis is associated with a mutation distant from the proteolytic cleavage site. Evidence for the functional importance of the triple helical model of spectrin","volume":"89","author":"Gallagher PG","year":"1992","unstructured":"PG Gallagher, et al., A common type of the spectrin alpha I 46-50a-kD peptide abnormality in hereditary elliptocytosis and pyropoikilocytosis is associated with a mutation distant from the proteolytic cleavage site. Evidence for the functional importance of the triple helical model of spectrin. 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