Structural basis for product specificities of MLL family methyltransferases

doi:10.1016/j.molcel.2022.08.022

	Structural basis for product specificities of MLL family methyltransferases
	Li, Yanjing 1,2; Zhao, Lijie 1,3; Zhang, Yuebin 4; Wu, Ping 5; Xu, Ying 1; Mencius, Jun 2; Zheng, Yongxin 2; Wang, Xiaoman 1,3; Xu, Wancheng 1,3; Huang, Naizhe 1,3; Ye, Xianwen6 ; Lei, Ming 7; Shi, Pan 8; Tian, Changlin 8; Peng, Chao 5; Li, Guohui 4; Liu, Zhijun 5; Quan, Shu 2; Chen, Yong1,3,6
	2022-10-20
发表期刊	MOLECULAR CELL (IF:14.5[JCR-2023],16.6[5-Year])
ISSN	1097-2765
EISSN	1097-4164
卷号	82 期号:20
发表状态	已发表
DOI	10.1016/j.molcel.2022.08.022
摘要	Human mixed-lineage leukemia (MLL) family methyltransferases methylate histone H3 lysine 4 to different methylation states (me1/me2/me3) with distinct functional outputs, but the mechanism underlying the different product specificities of MLL proteins remains unclear. Here, we develop methodologies to quantitatively measure the methylation rate difference between mono-, di-, and tri-methylation steps and demonstrate that MLL proteins possess distinct product specificities in the context of the minimum MLL-RBBP5-ASH2L complex. Comparative structural analyses of MLL complexes by X-ray crystal structures, fluorine-19 nuclear magnetic resonance, and molecular dynamics simulations reveal that the dynamics of two conserved tyrosine residues at the "F/Y (phenylalanine/tyrosine) switch"positions fine-tune the product specificity. The variation in the intramolecular interaction between SET-N and SET-C affects the F/Y switch dynamics, thus determining the product specificities of MLL proteins. These results indicate a modified F/Y switch rule applicable for most SET domain methyltransferases and implicate the functional divergence of MLL proteins.
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收录类别	SCI
语种	英语
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDB37010303] ; Shanghai Pilot Program for Basic Research - CAS Shanghai Branch[JCYJ-SHFY-2022-008] ; National Natural Science Foundation of China["31670748","31970576","32071195","31900934","21933010","31700647"] ; Young Elite Scientist Sponsorship Program by CAST[YESS20170198] ; National Postdoctoral Program for Innovative Talents[BX201700263] ; Construction and Operation of Zhangjiang Laboratory (II)[19DZ2260100] ; National Key R&D Program of China[2019YFA0709400] ; maintenance and reconstruction project[DSS-WXGZ-2020-0001]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000880784300010
出版者	CELL PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/251695
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_陈勇组
通讯作者	Peng, Chao; Li, Guohui; Liu, Zhijun; Quan, Shu; Chen, Yong
作者单位	1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Ctr Excellence Mol Cell Sci,State Key Lab Mol Biol, Shanghai 200031, Peoples R China 2.East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian 116023, Liaoning, Peoples R China 5.Chinese Acad Sci, Shanghai Adv Res Inst, Zhangjiang Lab, Natl Facil Prot Sci Shanghai, Shanghai 201210, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 7.Shanghai Jiao Tong Univ, Peoples Hosp 9, Shanghai Inst Precis Med, Sch Med, Shanghai 200025, Peoples R China 8.Univ Sci & Technol China, Affiliated Hosp USTC 1, Joint Ctr Biol Analyt Chem, Sch Life Sci,Div Life Sci & Med,Anhui Engn Lab Pep, Hefei 230026, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Yanjing,Zhao, Lijie,Zhang, Yuebin,et al. Structural basis for product specificities of MLL family methyltransferases[J]. MOLECULAR CELL,2022,82(20).
APA	Li, Yanjing.,Zhao, Lijie.,Zhang, Yuebin.,Wu, Ping.,Xu, Ying.,...&Chen, Yong.(2022).Structural basis for product specificities of MLL family methyltransferases.MOLECULAR CELL,82(20).
MLA	Li, Yanjing,et al."Structural basis for product specificities of MLL family methyltransferases".MOLECULAR CELL 82.20(2022).