{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:01:23Z","timestamp":1791201683837,"version":"4.2.0"},"reference-count":101,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,9,20]],"date-time":"2013-09-20T00:00:00Z","timestamp":1379635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>Abstract: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding.<\/jats:p>","DOI":"10.1002\/pro.2336","type":"journal-article","created":{"date-parts":[[2013,8,20]],"date-time":"2013-08-20T12:38:40Z","timestamp":1377002320000},"page":"1502-1518","source":"Crossref","is-referenced-by-count":33,"title":["Protein domain definition should allow for conditional disorder"],"prefix":"10.1002","volume":"22","author":[{"given":"Kavestri","family":"Yegambaram","sequence":"first","affiliation":[{"name":"School of Biological Sciences University of Auckland Private Bag 92019 Auckland 1142 New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther M.M.","family":"Bulloch","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Auckland Private Bag 92019 Auckland 1142 New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Kingston","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Auckland Private Bag 92019 Auckland 1142 New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060910-095130"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","unstructured":"LevittM(2009)Nature of the protein universe.Proc Natl Acad Sci USA106:11079\u201311084.","DOI":"10.1073\/pnas.0905029106"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2008.05.008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.31.082901.134314"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr948"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki034"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(97)00260-8"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80134-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60520-3"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60468-4"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","unstructured":"PorterLL RoseGD(2012)A thermodynamic definition of protein domains.Proc Natl Acad Sci USA109:9420\u20139425.","DOI":"10.1073\/pnas.1202604109"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","unstructured":"WetlauferDB(1973)Nucleation rapid folding and globular intrachain regions in proteins.Proc Natl Acad Sci USA70:697\u2013701.","DOI":"10.1073\/pnas.70.3.697"},{"key":"e_1_2_7_14_1","volume-title":"Introduction to protein structure","author":"Branden C","year":"1999"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201200116"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60460-X"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1228775"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200800151"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2011.03.014"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2008.12.003"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","unstructured":"StreetTO BolenDW RoseGD(2006)A molecular mechanism for osmolyte\u2010induced protein stability.Proc Natl Acad Sci USA103:13997\u201314002.","DOI":"10.1073\/pnas.0606236103"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.9.4831"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-06099-5_3"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.10.031"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300518200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"crossref","unstructured":"KingstonRL HamelDJ GayLS DahlquistFW MatthewsBW(2004)Structural basis for the attachment of a paramyxoviral polymerase to its template.Proc Natl Acad Sci USA101:8301\u20138306.","DOI":"10.1073\/pnas.0402690101"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00338-07"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja801332d"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.12.080"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.219857"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","unstructured":"JensenMR CommunieG RibeiroEA MartinezN DesfossesA SalmonL MollicaL GabelF JaminM LonghiS RuigrokRWH BlackledgeM. (2011)Intrinsic disorder in measles virus nucleocapsids.Proc Natl Acad Sci USA108:9839\u20139844.","DOI":"10.1073\/pnas.1103270108"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8630-8640.2004"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bb.24.060195.001041"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)89081-7"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.03.049"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.20.6097"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.10181"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308745200"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.10.029"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.108829"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(95)00227-W"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1634"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20052"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00504-09"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.05.015"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.03.073"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.333088"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/6\/1\/015001"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.1966.360040808"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bb.16.060187.000555"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-4622(96)02237-5"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(07)84010-6"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr960383c"},{"key":"e_1_2_7_54_1","doi-asserted-by":"crossref","unstructured":"GhoshK DillKA(2009)Computing protein stabilities from their chain lengths.Proc Natl Acad Sci USA106:10649\u201310654.","DOI":"10.1073\/pnas.0903995106"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410716200"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2009.06.004"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-381268-1.00015-X"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi300916v"},{"key":"e_1_2_7_59_1","first-page":"233","article-title":"NMR studies of partially folded molten\u2010globule states","volume":"278","author":"Redfield C","year":"2004","journal-title":"Methods Mol Biol"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409237509102551"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.368"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bb.18.060189.000403"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6107(96)00008-9"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0397-180"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb798"},{"key":"e_1_2_7_66_1","doi-asserted-by":"crossref","unstructured":"ScianM LinJC Le TrongI MakhatadzeGI StenkampRE AndersenNH(2012)Crystal and NMR structures of a Trp\u2010cage mini\u2010protein benchmark for computational fold prediction.Proc Natl Acad Sci USA109:12521\u201312525.","DOI":"10.1073\/pnas.1121421109"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00439a019"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560040809"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560061212"},{"key":"e_1_2_7_70_1","doi-asserted-by":"crossref","unstructured":"ChiuTK KubelkaJ Herbst\u2010IrmerR EatonWA HofrichterJ DaviesDR(2005)High\u2010resolution x\u2010ray crystal structures of the villin headpiece subdomain an ultrafast folding protein.Proc Natl Acad Sci USA102:7517\u20137522.","DOI":"10.1073\/pnas.0502495102"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.237"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360261104"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(00)76576-3"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja305300m"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/0079-6107(84)90008-7"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.752"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi002078y"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi100222h"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi049591m"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200402200"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2010.05.015"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011254402785"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560041120"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2011.06.004"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1988.10478639"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi970247h"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-367-7_2"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(07)84011-8"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(92)10003-V"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444993014374"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(97)76066-X"},{"key":"e_1_2_7_92_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444996012255"},{"key":"e_1_2_7_95_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511661686.031"},{"key":"e_1_2_7_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2009.11.002"},{"key":"e_1_2_7_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"},{"key":"e_1_2_7_98_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511819049.009"},{"key":"e_1_2_7_99_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a003851"},{"key":"e_1_2_7_100_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg292"},{"key":"e_1_2_7_101_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq720"},{"key":"e_1_2_7_102_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpro.2336","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpro.2336","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.2336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T11:36:14Z","timestamp":1694777774000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.2336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,20]]},"references-count":101,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1002\/pro.2336"],"URL":"https:\/\/doi.org\/10.1002\/pro.2336","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718080842.793487335","asserted-by":"object"}]},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,20]]}}}