Nickel(II) and Zinc(II) Binding to Tau Protein Fragments Containing Histidine and Cysteine

Nickel(II) and Zinc(II) Binding to Tau Protein Fragments Containing Histidine and Cysteine | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Nickel(II) and Zinc(II) Binding to Tau Protein Fragments Containing Histidine and Cysteine Faareha Mazhar, Noémi Piskolti, Viktória Kovács, Katalin Várnagy This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8834665/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Tau protein plays a crutial role in stablizing the neuronal microtubules in the human brain, under normal physiological environment. This protein contains 12 histidines and 2 cysteines, which are typically the primary metal binding sites. As the metal ions may participate in tau protein aggregation processes and the development of tauopathies, we characterized zinc(II) and nickel(II) complexes of tau fragments. The studied peptides were; tau(289-V300N) (Ac-SKCGSKDNIKHN-NH 2 ) containing Cys291 and His299, tau(288–293) (Ac-QSKCGS-NH 2 ) and tau(289–292) (Ac-SKCG-NH 2 ) containing only Cys291, as well as the single-His299 containing tau(292–301) (Ac-GSKDNIKHVP-NH 2 ) and its asparagine mutant at position 300. The pH potentiometric, UV-visible and CD spectroscopic measurements allowed us to understand the effect of these side chains on the stability and binding mode of metal ion complexes. For peptides containaing a single cysteine and single histidine, nickel(II) complexes with (N – ,N – ,N – ,S – ) and (N – ,N – ,N – ,N Im ) coordination modes were main species in alkaline media. UV-visible and CD spectroscopic curves showed that nickel(II) favours the cysteine binding site in the case of the tau (289–300) fragment. Through the polydentate coordination of this tau peptide, the stability of zinc(II) complex is significantly increased compared to fragments containing a single binding site. Cysteine histidine nickel(II) tau protein complex potentiometry UV-Vis and CD spectroscopy Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryinformationVarnagyK090226.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 08 Apr, 2026 Reviews received at journal 26 Mar, 2026 Reviews received at journal 23 Mar, 2026 Reviewers agreed at journal 05 Mar, 2026 Reviewers agreed at journal 05 Mar, 2026 Reviewers agreed at journal 04 Mar, 2026 Reviewers invited by journal 04 Mar, 2026 Editor assigned by journal 04 Mar, 2026 Submission checks completed at journal 04 Mar, 2026 First submitted to journal 09 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8834665","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":601468879,"identity":"135e5a40-8d5c-44b8-a728-d21f646371e8","order_by":0,"name":"Faareha Mazhar","email":"","orcid":"","institution":"University of Debrecen","correspondingAuthor":false,"prefix":"","firstName":"Faareha","middleName":"","lastName":"Mazhar","suffix":""},{"id":601468880,"identity":"1d1048da-d659-40db-93a9-2cf98bf92690","order_by":1,"name":"Noémi Piskolti","email":"","orcid":"","institution":"University of 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Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Cysteine, histidine, nickel(II), tau protein, complex, potentiometry, UV-Vis and CD spectroscopy","lastPublishedDoi":"10.21203/rs.3.rs-8834665/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8834665/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTau protein plays a crutial role in stablizing the neuronal microtubules in the human brain, under normal physiological environment. This protein contains 12 histidines and 2 cysteines, which are typically the primary metal binding sites. As the metal ions may participate in tau protein aggregation processes and the development of tauopathies, we characterized zinc(II) and nickel(II) complexes of tau fragments. The studied peptides were; tau(289-V300N) (Ac-SKCGSKDNIKHN-NH\u003csub\u003e2\u003c/sub\u003e) containing Cys291 and His299, tau(288\u0026ndash;293) (Ac-QSKCGS-NH\u003csub\u003e2\u003c/sub\u003e) and tau(289\u0026ndash;292) (Ac-SKCG-NH\u003csub\u003e2\u003c/sub\u003e) containing only Cys291, as well as the single-His299 containing tau(292\u0026ndash;301) (Ac-GSKDNIKHVP-NH\u003csub\u003e2\u003c/sub\u003e) and its asparagine mutant at position 300. The pH potentiometric, UV-visible and CD spectroscopic measurements allowed us to understand the effect of these side chains on the stability and binding mode of metal ion complexes. For peptides containaing a single cysteine and single histidine, nickel(II) complexes with (N\u003csup\u003e\u0026ndash;\u003c/sup\u003e,N\u003csup\u003e\u0026ndash;\u003c/sup\u003e,N\u003csup\u003e\u0026ndash;\u003c/sup\u003e,S\u003csup\u003e\u0026ndash;\u003c/sup\u003e) and (N\u003csup\u003e\u0026ndash;\u003c/sup\u003e,N\u003csup\u003e\u0026ndash;\u003c/sup\u003e,N\u003csup\u003e\u0026ndash;\u003c/sup\u003e,N\u003csub\u003eIm\u003c/sub\u003e) coordination modes were main species in alkaline media. UV-visible and CD spectroscopic curves showed that nickel(II) favours the cysteine binding site in the case of the tau (289\u0026ndash;300) fragment. Through the polydentate coordination of this tau peptide, the stability of zinc(II) complex is significantly increased compared to fragments containing a single binding site.\u003c/p\u003e","manuscriptTitle":"Nickel(II) and Zinc(II) Binding to Tau Protein Fragments Containing Histidine and Cysteine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-09 08:32:56","doi":"10.21203/rs.3.rs-8834665/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-09T02:10:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-26T19:55:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-23T08:32:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"121823539266543496612517647067158393115","date":"2026-03-05T19:57:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"9584406445978862908959104931801029485","date":"2026-03-05T12:20:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"100728232694104189414401199551926494962","date":"2026-03-04T19:19:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-04T14:23:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-04T13:12:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-04T06:34:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Biological Trace Element Research","date":"2026-02-09T22:07:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"biological-trace-element-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bter","sideBox":"Learn more about [Biological Trace Element Research](https://www.springer.com/journal/12011)","snPcode":"12011","submissionUrl":"https://submission.nature.com/new-submission/12011/3","title":"Biological Trace Element Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d9a676ac-f1df-4802-b960-69cdd1b30932","owner":[],"postedDate":"March 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T10:25:43+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-09 08:32:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8834665","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8834665","identity":"rs-8834665","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}