8WMS

Crystal structure of human DPPA3 in complex with human UHRF1 PHD domain

8WMS の概要

• エントリーDOI: 10.2210/pdb8wms/pdb
• 分子名称: E3 ubiquitin-protein ligase UHRF1, Developmental pluripotency-associated protein 3, ZINC ION (3 entities in total)
• 機能のキーワード: dna methylation, gene regulation
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12588.86

構造登録者

Shiraishi, N.,Arita, K. (登録日: 2023-10-04, 公開日: 2024-07-31, 最終更新日: 2025-03-19)

主引用文献

Shiraishi, N.,Konuma, T.,Chiba, Y.,Hokazono, S.,Nakamura, N.,Islam, M.H.,Nakanishi, M.,Nishiyama, A.,Arita, K.
Structure of human DPPA3 bound to the UHRF1 PHD finger reveals its functional and structural differences from mouse DPPA3.
Commun Biol, 7:746-746, 2024

PubMed Abstract: DNA methylation maintenance is essential for cell fate inheritance. In differentiated cells, this involves orchestrated actions of DNMT1 and UHRF1. In mice, the high-affinity binding of DPPA3 to the UHRF1 PHD finger regulates UHRF1 chromatin dissociation and cytosolic localization, which is required for oocyte maturation and early embryo development. However, the human DPPA3 ortholog functions during these stages remain unclear. Here, we report the structural basis for human DPPA3 binding to the UHRF1 PHD finger. The conserved human DPPA3 VRT motif binds to the acidic surface of UHRF1 PHD finger, whereas mouse DPPA3 binding additionally utilizes two unique α-helices. The binding affinity of human DPPA3 for the UHRF1 PHD finger was weaker than that of mouse DPPA3. Consequently, human DPPA3, unlike mouse DPPA3, failed to inhibit UHRF1 chromatin binding and DNA remethylation in Xenopus egg extracts effectively. Our data provide novel insights into the distinct function and structure of human DPPA3.

PubMed: 38898124
DOI: 10.1038/s42003-024-06434-9

実験手法

X-RAY DIFFRACTION (2.4 Å)