PT  - JOURNAL ARTICLE
AU  - Keiichi Hata
AU  - Naohiro Kobayashi
AU  - Keita Sugimura
AU  - Weihua Qin
AU  - Deis Haxholli
AU  - Yoshie Chiba
AU  - Gosuke Hayashi
AU  - Hiroki Onoda
AU  - Takahisa Ikegami
AU  - Christopher B. Mulholland
AU  - Atsuya Nishiyama
AU  - Makoto Nakanishi
AU  - Heinrich Leonhardt
AU  - Tsuyoshi Konuma
AU  - Kyohei Arita
TI  - Structural basis for the unique multifaceted interaction of DPPA3 with the UHRF1 PHD finger
AID  - 10.1101/2022.06.14.496052
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.14.496052
4099  - http://biorxiv.org/content/early/2022/06/14/2022.06.14.496052.short
4100  - http://biorxiv.org/content/early/2022/06/14/2022.06.14.496052.full
AB  - 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 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 solution nuclear magnetic resonance structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3. 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.Competing Interest StatementThe authors have declared no competing interest.