{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:29:43Z","timestamp":1791318583912,"version":"4.3.1"},"reference-count":109,"publisher":"National Academy of Sciences","issue":"43","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,10,28]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Mutations in human Cu, Zn superoxide dismutase (SOD) cause the motor neuron disease ALS. To better understand why, we compared the aggregation, metal binding, and conformational dynamics of normal and mutant SOD proteins by using the biophysical techniques of X-ray scattering, inductively coupled plasma MS, and ESR spectroscopy. For SOD proteins with defects at a mutational hotspot, we found that copper deficiency, flexibility, and aggregation paralleled clinical severity in ALS patients. These data support a unifying protein framework destabilization mechanism for SOD-linked ALS and thereby point to potential therapies for this lethal condition with few treatment options.<\/jats:p>","DOI":"10.1073\/pnas.1308531111","type":"journal-article","created":{"date-parts":[[2014,10,15]],"date-time":"2014-10-15T01:09:33Z","timestamp":1413335373000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":71,"title":["Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes"],"prefix":"10.1073","volume":"111","author":[{"given":"Ashley J.","family":"Pratt","sequence":"first","affiliation":[{"name":"Department of Integrative Structural and Computational Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037;"},{"name":"Life Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037;"},{"name":"Life Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory E.","family":"Merz","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Rambo","sequence":"additional","affiliation":[{"name":"Physical Biosciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Andrew","family":"Lancaster","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Georgia, Athens, GA 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin N.","family":"Dyer","sequence":"additional","affiliation":[{"name":"Physical Biosciences Divisions, Lawrence Berkeley National Laboratory, Berkeley, CA 94720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Borbat","sequence":"additional","affiliation":[{"name":"Center for Advanced ESR Studies (ACERT), Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"Farris L.","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Georgia, Athens, GA 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W. W.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Georgia, Athens, GA 30602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack H.","family":"Freed","sequence":"additional","affiliation":[{"name":"Center for Advanced ESR Studies (ACERT), Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Crane","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Tainer","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037;"},{"name":"Life Sciences and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth D.","family":"Getzoff","sequence":"additional","affiliation":[{"name":"Department of Integrative Structural and Computational Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,10,14]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"1","article-title":"Amyotrophic lateral sclerosis: Update and new developments","volume":"2012","author":"Pratt AJ","year":"2012","unstructured":"AJ Pratt, ED Getzoff, JJ Perry, Amyotrophic lateral sclerosis: Update and new developments. Degener Neurol Neuromuscul Dis 2012, 1\u201314 (2012).","journal-title":"Degener Neurol Neuromuscul Dis"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8351519"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/362059a0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-996-0008-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340050408"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)63504-5"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2009.11.004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8209258"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199655100-00009"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199604000-00011"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0939-7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80272-X"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.36.4.511"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060170"},{"key":"e_1_3_3_15_2","first-page":"283","volume-title":"European Handbook of Neurological Management","author":"Andersen PM","year":"2011","unstructured":"PM Andersen, European Handbook of Neurological Management, eds NE Gilhus, MP Barnes, M Brainin (Wiley-Blackwell, Oxford), pp. 283\u2013310 (2011)."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/364584a0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5248.515"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108585200"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5709"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00889-1"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.220417997"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5384.1851"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1237797100"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)77291-8"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.11.031"},{"key":"e_1_3_3_26_2","first-page":"417","volume-title":"Advanced Understanding of Neurodegenerative Diseases","author":"Shin DS","year":"2011","unstructured":"DS Shin, AJ Pratt, ED Getzoff, JJ Perry Advanced Understanding of Neurodegenerative Diseases, ed RC-C Chang (InTech, Rijeka, Croatia), pp. 417\u2013442 (2011)."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602048103"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809845106"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-011-0679-8"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2660"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800564200"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115402109"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704307104"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.13.6109"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)81443-3"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45784-5"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.3109\/17482968.2012.656311"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.08.024"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.07.043"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)44055-6"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.05.003"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0210802"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(03)00355-3"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703857104"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802083200"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509496200"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2002.0498"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.113696"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0646-5"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.12.029"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1042\/bse0560149"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)01090-2"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(82)90174-7"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22157"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812297106"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.04.003"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2010.03.012"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2009.12.015"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-083012-130301"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583507004635"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.6.2574"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1353"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.272641"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.01.080"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.21638"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2453"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.4149\/gpb_2009_02_174"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq461"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2011.11.005"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09265"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2004.06.006"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007750050363"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90956-3"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.805"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.2119\/2007-00036.Maret"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69051936.x"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10405"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cplett.2009.09.042"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305143101"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi500158w"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112088200"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.12.024"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807058105"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907387106"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(85)90380-7"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.04.027"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00110"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4196-13.2014"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112087200"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.2.1007"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0720422.x"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2001.0443"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000355"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610923104"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.01.005"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn823"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi900703v"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.07.068"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp260"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913021108"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.086074"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2012.04.016"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi200614y"},{"key":"e_1_3_3_104_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)83727-9"},{"key":"e_1_3_3_105_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi951892w"},{"key":"e_1_3_3_106_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(78)53044-9"},{"key":"e_1_3_3_107_2","volume-title":"Current Protocols in Chemical Biology","author":"Vaccaro BJ","year":"2009","unstructured":"BJ Vaccaro, AL Menon, WA Lancaster, MWW Adams Current Protocols in Chemical Biology (Wiley, New York, 2009)."},{"key":"e_1_3_3_108_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889812048698"},{"key":"e_1_3_3_109_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmre.1997.1201"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1308531111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:11:06Z","timestamp":1649801466000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1308531111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,14]]},"references-count":109,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2014,10,28]]}},"alternative-id":["10.1073\/pnas.1308531111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1308531111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,14]]},"assertion":[{"value":"2014-10-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}