{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T16:40:06Z","timestamp":1766940006677},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The sequence of a protein chain determines both its conformation and its function in vivo. An attempt is made to gain an understanding of the classes of deformations that can arise in an important structural motif, the \u03b1\u2010helical coiled coil, as a consequence of mutations occurring in its underlying heptad substructure. In order to do so we consider the model structure of segment 1A in intermediate filaments and then investigate the structures arising from each of the 22 mutations observed in cytokeratin K5\/K14 molecules that lead to variants of epidermolysis bullosa simplex. These are refined separately using a molecular dynamics protocol. The mutations often result in a significant distortion of the backbone over a turn or so of the \u03b1 helix in either the chain itself or its constituent partner, leading to the likelihood of impaired chain aggregation and hence molecular assembly. One mutant (K14\u2010L143P; 1A\u201028) gave rise to structural distortion along almost the entire length of segment 1A. The remaining structures showed less deformation, and normal\u2010looking intermediate filaments are likely in vivo. In addition, an identical mutation in the same position in each of the chains in the heterodimer did not necessarily give equivalent structural distortions. Although proline mutations frequently lead to the most severe structural deformations, a non\u2010proline substitution (K14\u2010R125S; 1A\u201010) gave rise to the largest local structural disruption that was observed. Unexpectedly, mutations in positions <jats:italic>a<\/jats:italic> and <jats:italic>d<\/jats:italic> were not always of the greatest structural significance, although three in position <jats:italic>a<\/jats:italic> were shown by AGADIR to result in a significant increase in \u03b1\u2010helix stability. Proteins 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.20089","type":"journal-article","created":{"date-parts":[[2004,4,2]],"date-time":"2004-04-02T00:00:54Z","timestamp":1080864054000},"page":"1043-1052","source":"Crossref","is-referenced-by-count":31,"title":["Modeling effects of mutations in coiled\u2010coil structures: Case study using epidermolysis bullosa simplex mutations in segment 1a of k5\/k14 intermediate filaments"],"prefix":"10.1002","volume":"55","author":[{"given":"Thomasin A.","family":"Smith","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter M.","family":"Steinert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.D.","family":"Parry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,4]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0365110X53001964"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/171059a0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4545"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1948029"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01801"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3719"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00100-3"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.131219198"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb1194-789"},{"key":"e_1_2_7_11_2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/343531a0","article-title":"Macrophage scavenger receptor\u2010type I: a trimer of \u03b1\u2010helical and collagen\u2010like coiled\u2010coils","volume":"343","author":"Kodama T","year":"1990","journal-title":"Nature (Lond)"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/79006"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.761"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/371080a0"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8248779"},{"key":"e_1_2_7_16_2","first-page":"1","volume-title":"Intermediate filament structure","author":"Parry DAD","year":"1995"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583500003516"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2002.4437"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.6.1255"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2002.4438"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4442"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90051-Y"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0493-327"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.7.1171"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12323846"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12342985"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)8:1<57::AID-HUMU8>3.0.CO;2-M"},{"key":"e_1_2_7_28_2","first-page":"405","article-title":"Novel mutations in the 1A helical domain of K5 and K14 are involved in a mild epidermolysis bullosa simplex (EBS) phenotype","volume":"109","author":"Liovic M","year":"1997","journal-title":"J Invest Dermatol"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12286486"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2000.03304.x"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00388.x"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00495.x"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(200005)20:5<371::AID-PD818>3.0.CO;2-5"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01508.x"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.01334.x"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(82)90424-X"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90034-X"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3197"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00196781"},{"key":"e_1_2_7_40_2","unstructured":"RousselA InisanAG Knoops\u2010MouthyE CambilauC. 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