دورية أكاديمية
Structural basis for the unique multifaceted interaction of DPPA3 with the UHRF1 PHD finger.
العنوان: | Structural basis for the unique multifaceted interaction of DPPA3 with the UHRF1 PHD finger. |
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المؤلفون: | Hata K; Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan., Kobayashi N; RIKEN Center for Biosystems Dynamics Research, Suehiro-cho 1-7-22, Tsurumi, Yokohama, Kanagawa 230-0045, Japan., Sugimura K; Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan., Qin W; Faculty of Biology, Ludwig-Maximilians-Universität München, Munich, Germany., Haxholli D; Faculty of Biology, Ludwig-Maximilians-Universität München, Munich, Germany., Chiba Y; Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan., Yoshimi S; Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan., Hayashi G; Department of Biomolecular Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan., Onoda H; Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan., Ikegami T; Structural Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan., Mulholland CB; Faculty of Biology, Ludwig-Maximilians-Universität München, Munich, Germany., Nishiyama A; Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan., Nakanishi M; Division of Cancer Cell Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan., Leonhardt H; Faculty of Biology, Ludwig-Maximilians-Universität München, Munich, Germany., Konuma T; Structural Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan., Arita K; Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. |
المصدر: | Nucleic acids research [Nucleic Acids Res] 2022 Nov 28; Vol. 50 (21), pp. 12527-12542. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1992- : Oxford : Oxford University Press Original Publication: London, Information Retrieval ltd. |
مواضيع طبية MeSH: | CCAAT-Enhancer-Binding Proteins*/metabolism , PHD Zinc Fingers*, Mice ; Animals ; Ubiquitin-Protein Ligases/metabolism ; Chromatin ; DNA Methylation ; Chromosomal Proteins, Non-Histone/metabolism |
مستخلص: | Ubiquitin-like with PHD and RING finger domain-containing protein 1 (UHRF1)-dependent DNA methylation is essential for maintaining cell fate during cell proliferation. Developmental pluripotency-associated 3 (DPPA3) is an intrinsically disordered protein that specifically interacts with UHRF1 and promotes passive DNA demethylation by inhibiting UHRF1 chromatin localization. However, the molecular basis of how DPPA3 interacts with and inhibits UHRF1 remains unclear. We aimed to determine the structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3 using nuclear magnetic resonance. Induced α-helices in DPPA3 upon binding of UHRF1 PHD contribute to stable complex formation with multifaceted interactions, unlike canonical ligand proteins of the PHD domain. Mutations in the binding interface and unfolding of the DPPA3 helical structure inhibited binding to UHRF1 and its chromatin localization. Our results provide structural insights into the mechanism and specificity underlying the inhibition of UHRF1 by DPPA3. (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.) |
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المشرفين على المادة: | 0 (CCAAT-Enhancer-Binding Proteins) EC 2.3.2.27 (Ubiquitin-Protein Ligases) 0 (Chromatin) 0 (Dppa3 protein, mouse) 0 (Chromosomal Proteins, Non-Histone) EC 2.3.2.27 (Uhrf1 protein, mouse) |
تواريخ الأحداث: | Date Created: 20221124 Date Completed: 20221220 Latest Revision: 20221223 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC9757060 |
DOI: | 10.1093/nar/gkac1082 |
PMID: | 36420895 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1362-4962 |
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DOI: | 10.1093/nar/gkac1082 |