Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation

Satomi Kori; Laure Ferry; Shohei Matano; Tomohiro Jimenji; Noriyuki Kodera; Takeshi Tsusaka; Rumie Matsumura; Takashi Oda; Mamoru Sato; Naoshi Dohmae; Toshio Ando; Yoichi Shinkai; Pierre Antoine Defossez; Kyohei Arita

doi:10.1016/j.str.2018.11.012

Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation

Satomi Kori
, Laure Ferry
, Shohei Matano
, Tomohiro Jimenji
, Noriyuki Kodera
, Takeshi Tsusaka
, Rumie Matsumura
, Takashi Oda
, Mamoru Sato
, Naoshi Dohmae
, Toshio Ando
, Yoichi Shinkai
, Pierre Antoine Defossez
, Kyohei Arita

Yokohama City University
Paris Descartes University
Kanazawa University
WPI Nano Life Science Institute
Japan Science and Technology Corporation (JST)
RIKEN Cluster for Pioneering Research
RIKEN Center for Sustainable Resource Science

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

The protein UHRF1 is crucial for DNA methylation maintenance. The tandem Tudor domain (TTD) of UHRF1 binds histone H3K9me2/3 with micromolar affinity, as well as unmethylated linker regions within UHRF1 itself, causing auto-inhibition. Recently, we showed that a methylated histone-like region of DNA ligase 1 (LIG1K126me2/me3) binds the UHRF1 TTD with nanomolar affinity, permitting UHRF1 recruitment to chromatin. Here we report the crystal structure of the UHRF1 TTD bound to a LIG1K126me3 peptide. The data explain the basis for the high TTD-binding affinity of LIG1K126me3 and reveal that the interaction may be regulated by phosphorylation. Binding of LIG1K126me3 switches the overall structure of UHRF1 from a closed to a flexible conformation, suggesting that auto-inhibition is relieved. Our results provide structural insight into how UHRF1 performs its key function in epigenetic maintenance.

Original language	English
Pages (from-to)	485-496.e7
Journal	Structure
Volume	27
Issue number	3
DOIs	https://doi.org/10.1016/j.str.2018.11.012
Publication status	Published - 5 Mar 2019
Externally published	Yes

Keywords

DNA methylation
Tudor domain
UHRF1
X-ray crystallography
chromatin
lysine methylation
small-angle X-ray scattering

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10.1016/j.str.2018.11.012

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Kori, S., Ferry, L., Matano, S., Jimenji, T., Kodera, N., Tsusaka, T., Matsumura, R., Oda, T., Sato, M., Dohmae, N., Ando, T., Shinkai, Y., Defossez, P. A., & Arita, K. (2019). Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation. Structure, 27(3), 485-496.e7. https://doi.org/10.1016/j.str.2018.11.012

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title = "Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation",

abstract = "The protein UHRF1 is crucial for DNA methylation maintenance. The tandem Tudor domain (TTD) of UHRF1 binds histone H3K9me2/3 with micromolar affinity, as well as unmethylated linker regions within UHRF1 itself, causing auto-inhibition. Recently, we showed that a methylated histone-like region of DNA ligase 1 (LIG1K126me2/me3) binds the UHRF1 TTD with nanomolar affinity, permitting UHRF1 recruitment to chromatin. Here we report the crystal structure of the UHRF1 TTD bound to a LIG1K126me3 peptide. The data explain the basis for the high TTD-binding affinity of LIG1K126me3 and reveal that the interaction may be regulated by phosphorylation. Binding of LIG1K126me3 switches the overall structure of UHRF1 from a closed to a flexible conformation, suggesting that auto-inhibition is relieved. Our results provide structural insight into how UHRF1 performs its key function in epigenetic maintenance.",

keywords = "DNA methylation, Tudor domain, UHRF1, X-ray crystallography, chromatin, lysine methylation, small-angle X-ray scattering",

author = "Satomi Kori and Laure Ferry and Shohei Matano and Tomohiro Jimenji and Noriyuki Kodera and Takeshi Tsusaka and Rumie Matsumura and Takashi Oda and Mamoru Sato and Naoshi Dohmae and Toshio Ando and Yoichi Shinkai and Defossez, \{Pierre Antoine\} and Kyohei Arita",

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year = "2019",

month = mar,

day = "5",

doi = "10.1016/j.str.2018.11.012",

language = "English",

volume = "27",

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Kori, S, Ferry, L, Matano, S, Jimenji, T, Kodera, N, Tsusaka, T, Matsumura, R, Oda, T, Sato, M, Dohmae, N, Ando, T, Shinkai, Y, Defossez, PA & Arita, K 2019, 'Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation', Structure, vol. 27, no. 3, pp. 485-496.e7. https://doi.org/10.1016/j.str.2018.11.012

TY - JOUR

T1 - Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation

AU - Kori, Satomi

AU - Ferry, Laure

AU - Matano, Shohei

AU - Jimenji, Tomohiro

AU - Kodera, Noriyuki

AU - Tsusaka, Takeshi

AU - Matsumura, Rumie

AU - Oda, Takashi

AU - Sato, Mamoru

AU - Dohmae, Naoshi

AU - Ando, Toshio

AU - Shinkai, Yoichi

AU - Defossez, Pierre Antoine

AU - Arita, Kyohei

PY - 2019/3/5

Y1 - 2019/3/5

N2 - The protein UHRF1 is crucial for DNA methylation maintenance. The tandem Tudor domain (TTD) of UHRF1 binds histone H3K9me2/3 with micromolar affinity, as well as unmethylated linker regions within UHRF1 itself, causing auto-inhibition. Recently, we showed that a methylated histone-like region of DNA ligase 1 (LIG1K126me2/me3) binds the UHRF1 TTD with nanomolar affinity, permitting UHRF1 recruitment to chromatin. Here we report the crystal structure of the UHRF1 TTD bound to a LIG1K126me3 peptide. The data explain the basis for the high TTD-binding affinity of LIG1K126me3 and reveal that the interaction may be regulated by phosphorylation. Binding of LIG1K126me3 switches the overall structure of UHRF1 from a closed to a flexible conformation, suggesting that auto-inhibition is relieved. Our results provide structural insight into how UHRF1 performs its key function in epigenetic maintenance.

AB - The protein UHRF1 is crucial for DNA methylation maintenance. The tandem Tudor domain (TTD) of UHRF1 binds histone H3K9me2/3 with micromolar affinity, as well as unmethylated linker regions within UHRF1 itself, causing auto-inhibition. Recently, we showed that a methylated histone-like region of DNA ligase 1 (LIG1K126me2/me3) binds the UHRF1 TTD with nanomolar affinity, permitting UHRF1 recruitment to chromatin. Here we report the crystal structure of the UHRF1 TTD bound to a LIG1K126me3 peptide. The data explain the basis for the high TTD-binding affinity of LIG1K126me3 and reveal that the interaction may be regulated by phosphorylation. Binding of LIG1K126me3 switches the overall structure of UHRF1 from a closed to a flexible conformation, suggesting that auto-inhibition is relieved. Our results provide structural insight into how UHRF1 performs its key function in epigenetic maintenance.

KW - DNA methylation

KW - Tudor domain

KW - UHRF1

KW - X-ray crystallography

KW - chromatin

KW - lysine methylation

KW - small-angle X-ray scattering

U2 - 10.1016/j.str.2018.11.012

DO - 10.1016/j.str.2018.11.012

M3 - Article

C2 - 30639225

AN - SCOPUS:85061660551

SN - 0969-2126

VL - 27

SP - 485-496.e7

JO - Structure

JF - Structure

IS - 3

ER -

Structure of the UHRF1 Tandem Tudor Domain Bound to a Methylated Non-histone Protein, LIG1, Reveals Rules for Binding and Regulation

Abstract

Keywords

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