{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:57:08Z","timestamp":1790427428241,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"67","license":[{"start":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T00:00:00Z","timestamp":1510704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["EMR\/2015\/000111"],"award-info":[{"award-number":["EMR\/2015\/000111"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Direct binding of divalent metal ion, especially Zn<jats:sup>2+<\/jats:sup>, have been shown to increase the rate of tau aggregation and enhance tau toxicity in cells. Hence, understanding the molecular basis of the Zn<jats:sup>2+<\/jats:sup>\u2010accelerated tau aggregation can potentially determine the molecular interactions modulating tau aggregation. Herein, we show that Zn<jats:sup>2+<\/jats:sup> coordinates through the cysteine in R3 repeat and significantly accelerates the aggregation rate of the three repeat tau constructs (K19) but that the coordination is incapable of increasing the aggregation rate of the 20\u2005amino acid peptide derived from the R3 repeat (R3) of tau. The NMR characterization of the binding of Zn<jats:sup>2+<\/jats:sup> to K19, together with the aggregation studies with K19, R3 and R4 peptides, reveal the presence of an aggregation\u2010inhibitory interaction between the R3 and R4 repeat of K19. Our data show that binding of Zn<jats:sup>2+<\/jats:sup> to R3 repeat of tau, weaken the aggregation\u2010inhibiting influence between R3 and R4 repeats, leading to faster aggregation of tau protein.<\/jats:p>","DOI":"10.1002\/chem.201704555","type":"journal-article","created":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T08:12:43Z","timestamp":1508227963000},"page":"16976-16979","source":"Crossref","is-referenced-by-count":34,"title":["Zn<sup>2+<\/sup> Interrupts R4\u2010R3 Association Leading to Accelerated Aggregation of Tau Protein"],"prefix":"10.1002","volume":"23","author":[{"given":"A. C.","family":"Jiji","sequence":"first","affiliation":[{"name":"School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER TVM) Maruthamala P.O  Thiruvananthapuram-695551 Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Arshad","sequence":"additional","affiliation":[{"name":"School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER TVM) Maruthamala P.O  Thiruvananthapuram-695551 Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. R.","family":"Dhanya","sequence":"additional","affiliation":[{"name":"School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER TVM) Maruthamala P.O  Thiruvananthapuram-695551 Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. S.","family":"Shabana","sequence":"additional","affiliation":[{"name":"School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER TVM) Maruthamala P.O  Thiruvananthapuram-695551 Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. K.","family":"Mehjubin","sequence":"additional","affiliation":[{"name":"School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER TVM) Maruthamala P.O  Thiruvananthapuram-695551 Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-1860","authenticated-orcid":false,"given":"Vinesh","family":"Vijayan","sequence":"additional","affiliation":[{"name":"School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram (IISER TVM) Maruthamala P.O  Thiruvananthapuram-695551 Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,15]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1899488"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1121"},{"key":"e_1_2_2_4_1","unstructured":"\u00a0"},{"key":"e_1_2_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.11.4051"},{"key":"e_1_2_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206334200"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi052530j"},{"key":"e_1_2_2_8_1","unstructured":"\u00a0"},{"key":"e_1_2_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105196200"},{"key":"e_1_2_2_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja110545h"},{"key":"e_1_2_2_11_1","unstructured":"\u00a0"},{"key":"e_1_2_2_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja7100517"},{"key":"e_1_2_2_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja305470p"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23002"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/383550a0"},{"key":"e_1_2_2_16_1","unstructured":"\u00a0"},{"key":"e_1_2_2_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi800783d"},{"key":"e_1_2_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvg116"},{"key":"e_1_2_2_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi980537d"},{"key":"e_1_2_2_20_1","unstructured":"\u00a0"},{"key":"e_1_2_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0618649"},{"key":"e_1_2_2_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja107842f"},{"key":"e_1_2_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.12.008"},{"key":"e_1_2_2_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.6b01733"},{"key":"e_1_2_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.06.062"},{"key":"e_1_2_2_26_1","unstructured":"\u00a0"},{"key":"e_1_2_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.16.4361"},{"key":"e_1_2_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302212110"},{"key":"e_1_2_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(98)00092-6"},{"key":"e_1_2_2_30_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.12.1685"},{"key":"e_1_2_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410310310"},{"key":"e_1_2_2_32_1","unstructured":"\u00a0"},{"key":"e_1_2_2_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi8008856"},{"key":"e_1_2_2_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.058883"},{"key":"e_1_2_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.11.022"},{"key":"e_1_2_2_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.06.047"},{"key":"e_1_2_2_37_1","unstructured":"\u00a0"},{"key":"e_1_2_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201606544"},{"key":"e_1_2_2_38_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201606544"},{"key":"e_1_2_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201508968"},{"key":"e_1_2_2_39_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201508968"},{"key":"e_1_2_2_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2754"},{"key":"e_1_2_2_41_1","unstructured":"\u00a0"},{"key":"e_1_2_2_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr050361j"},{"key":"e_1_2_2_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr800556u"},{"key":"e_1_2_2_44_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.125211"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.201704555","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.201704555","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:06:30Z","timestamp":1760299590000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.201704555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,15]]},"references-count":46,"journal-issue":{"issue":"67","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1002\/chem.201704555"],"URL":"https:\/\/doi.org\/10.1002\/chem.201704555","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,15]]}}}