{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:02:48Z","timestamp":1788498168881,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:00:00Z","timestamp":1606608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["19-34-51043"],"award-info":[{"award-number":["19-34-51043"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["18-15-00357"],"award-info":[{"award-number":["18-15-00357"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015261","name":"Ambassade de France \u00e0 Moscou","doi-asserted-by":"publisher","award":["Metchnikov program"],"award-info":[{"award-number":["Metchnikov program"]}],"id":[{"id":"10.13039\/501100015261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transactive response DNA and RNA binding protein 43 kDa (TDP-43) is a highly conserved heterogeneous nuclear ribonucleoprotein (hnRNP), which is involved in several steps of protein production including transcription and splicing. Its aggregates are frequently observed in motor neurons from amyotrophic lateral sclerosis patients and in the most common variant of frontotemporal lobar degeneration. Recently it was shown that TDP-43 is able to bind Zn2+ by its RRM domain. In this work, we have investigated Zn2+ binding to a short peptide 256\u2013264 from C-terminus of RRM2 domain using isothermal titration calorimetry, electrospray ionization mass spectrometry, QM\/MM simulations, and NMR spectroscopy. We have found that this peptide is able to bind zinc ions with a Ka equal to 1.6 \u00d7 105 M\u22121. Our findings suggest the existence of a zinc binding site in the C-terminal region of RRM2 domain. Together with the existing structure of the RRM2 domain of TDP-43 we propose a model of its complex with Zn2+ which illustrates how zinc might regulate DNA\/RNA binding.<\/jats:p>","DOI":"10.3390\/ijms21239080","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T21:00:57Z","timestamp":1606683657000},"page":"9080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Zinc Binds to RRM2 Peptide of TDP-43"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8908-4268","authenticated-orcid":false,"given":"Andrey V.","family":"Golovin","sequence":"first","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, 119234 Moscow, Russian"},{"name":"Sirius University of Science and Technology, 354340 Sochi, Russian"},{"name":"Faculty of Computer Science, National Research University Higher School of Economics, 101000 Moscow, Russian"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5990-8898","authenticated-orcid":false,"given":"Francois","family":"Devred","sequence":"additional","affiliation":[{"name":"Inst Neurophysiopathol, CNRS, INP, Aix Marseille Universit\u00e9, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahbia","family":"Yatoui","sequence":"additional","affiliation":[{"name":"Inst Neurophysiopathol, CNRS, INP, Aix Marseille Universit\u00e9, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei Yu.","family":"Roman","sequence":"additional","affiliation":[{"name":"Inst Neurophysiopathol, CNRS, INP, Aix Marseille Universit\u00e9, 13385 Marseille, France"},{"name":"Institute of Physiologically Active Compounds, RAS, 142432 Chernogolovka, Russian"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-8119","authenticated-orcid":false,"given":"Arthur O.","family":"Zalevsky","sequence":"additional","affiliation":[{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, 119234 Moscow, Russian"},{"name":"Sirius University of Science and Technology, 354340 Sochi, Russian"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remy","family":"Puppo","sequence":"additional","affiliation":[{"name":"Plate-forme Prot\u00e9omique, Institut de Microbiologie de la M\u00e9diterran\u00e9e (IMM), CNRS FR 3479, Aix-Marseille Universit\u00e9, Marseille Prot\u00e9omique (MaP), 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-9013","authenticated-orcid":false,"given":"Regine","family":"Lebrun","sequence":"additional","affiliation":[{"name":"Plate-forme Prot\u00e9omique, Institut de Microbiologie de la M\u00e9diterran\u00e9e (IMM), CNRS FR 3479, Aix-Marseille Universit\u00e9, Marseille Prot\u00e9omique (MaP), 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francoise","family":"Guerlesquin","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Ing\u00e9nierie des Syst\u00e8mes Macromol\u00e9culaires, UMR 7255, Institut de Microbiologie de la M\u00e9diterran\u00e9e, CNRS, Aix-Marseille Universit\u00e9, 13009 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp O.","family":"Tsvetkov","sequence":"additional","affiliation":[{"name":"Inst Neurophysiopathol, CNRS, INP, Aix Marseille Universit\u00e9, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1038\/cddiscovery.2017.71","article-title":"Zinc-finger proteins in health and disease","volume":"3","author":"Cassandri","year":"2017","journal-title":"Cell Death Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"L84","DOI":"10.1016\/j.bpj.2010.09.015","article-title":"Minimal Zn(2+) binding site of amyloid-\u03b2","volume":"99","author":"Tsvetkov","year":"2010","journal-title":"Biophys. 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