Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46

Mahana, Yutaka; Ariyoshi, Mariko; Nozawa, Ryu-Suke; Shibata, Sachiko; Nagao, Koji; Obuse, Chikashi; Shirakawa, Masahiro

doi:https://doi.org/10.1016/j.str.2023.12.001

Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46

Mahana, Yutaka; Ariyoshi, Mariko; Nozawa, Ryu-Suke et al.

Structure, 2024, 32(3), 304-315.e5

Number of Access:649（2025-09-06 05:11 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/95866

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Title	Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46
Creator	CreatorName Mahana, Yutaka
	NRID 1000080437243 1000080437243 ORCID 0000-0002-1361-2642 0000-0002-1361-2642 researchmap permalink 7000010594 7000010594 Scopus Author ID 7006547610 7006547610 CreatorName Ariyoshi, Mariko
	CreatorName Nozawa, Ryu-Suke
	CreatorName Shibata, Sachiko
	NRID 1000060426575 1000060426575 researchmap permalink kngo kngo Scopus Author ID 35727011600 35727011600 CreatorName Nagao, Koji
	NRID 1000000273855 1000000273855 researchmap permalink obuse obuse Scopus Author ID 6701730728 6701730728 CreatorName Obuse, Chikashi
	NRID 1000000202119 1000000202119 CreatorName Shirakawa, Masahiro
Subject	C11orf46
	heterochromatin
	histone methyltransferase
	methyl-CpG-binding domain
	SETDB1
	SETDB2
Description	Mahana Y., Ariyoshi M., Nozawa R.S., et al. Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46. Structure 32, 304 (2024); https://doi.org/10.1016/j.str.2023.12.001.
Abstract	SETDB1 and SETDB2 mediate trimethylation of histone H3 lysine 9 (H3K9), an epigenetic hallmark of repressive chromatin. They contain a non-canonical methyl-CpG-binding domain (MBD) and bifurcated SET domain, implying interplay between H3K9 trimethylation and DNA methylation in SETDB functions. Here, we report the crystal structure of human SETDB2 MBD bound to the cysteine-rich domain of a zinc-binding protein, C11orf46. SETDB2 MBD comprises the conserved MBD core and a unique N-terminal extension. Although the MBD core has the conserved basic concave surface for DNA binding, it utilizes it for recognition of the cysteine-rich domain of C11orf46. This interaction involves the conserved arginine finger motif and the unique N-terminal extension of SETDB2 MBD, with a contribution from intermolecular β-sheet formation. Thus, the non-canonical MBD of SETDB1/2 seems to have lost methylated DNA-binding ability but gained a protein-protein interaction surface. Our findings provide insight into the molecular assembly of SETDB-associated repression complexes.
Publisher	Cell Press
Source Title	Structure
Volume (Issue)	32(3)
Page	304-315.e5
Date of Issued	2024-03-07
Language	English
Handle URL	https://hdl.handle.net/11094/95866
PISSN	09692126
eISSN	18784186
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1016/j.str.2023.12.001
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Structure. 2024, 32(3), p. 304-315.e5
DC.title	Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46
DC.creator	Mahana, Yutaka
	Ariyoshi, Mariko
	Nozawa, Ryu-Suke
	Shibata, Sachiko
	Nagao, Koji
	Obuse, Chikashi
	Shirakawa, Masahiro
DC.publisher	Cell Press
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-03-07
DC.identifier	https://doi.org/10.1016/j.str.2023.12.001
DC.subject	C11orf46
	heterochromatin
	histone methyltransferase
	methyl-CpG-binding domain
	SETDB1
	SETDB2
DC.description	Mahana Y., Ariyoshi M., Nozawa R.S., et al. Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46. Structure 32, 304 (2024); https://doi.org/10.1016/j.str.2023.12.001.
DCTERMS.abstract	SETDB1 and SETDB2 mediate trimethylation of histone H3 lysine 9 (H3K9), an epigenetic hallmark of repressive chromatin. They contain a non-canonical methyl-CpG-binding domain (MBD) and bifurcated SET domain, implying interplay between H3K9 trimethylation and DNA methylation in SETDB functions. Here, we report the crystal structure of human SETDB2 MBD bound to the cysteine-rich domain of a zinc-binding protein, C11orf46. SETDB2 MBD comprises the conserved MBD core and a unique N-terminal extension. Although the MBD core has the conserved basic concave surface for DNA binding, it utilizes it for recognition of the cysteine-rich domain of C11orf46. This interaction involves the conserved arginine finger motif and the unique N-terminal extension of SETDB2 MBD, with a contribution from intermolecular β-sheet formation. Thus, the non-canonical MBD of SETDB1/2 seems to have lost methylated DNA-binding ability but gained a protein-protein interaction surface. Our findings provide insight into the molecular assembly of SETDB-associated repression complexes.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	95866
citation_title	Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46
citation_author	Mahana, Yutaka
	Ariyoshi, Mariko
	Nozawa, Ryu-Suke
	Shibata, Sachiko
	Nagao, Koji
	Obuse, Chikashi
	Shirakawa, Masahiro
citation_publisher	Cell Press
citation_language	English
citation_date	2024-03-07
citation_journal_title	Structure
citation_volume	32
citation_issue	3
citation_firstpage	304
citation_lastpage	315.e5
citation_doi	https://doi.org/10.1016/j.str.2023.12.001
citation_public_url	https://hdl.handle.net/11094/95866

Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46

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