solutionstructureofthernarecognitiondomainofmettl3mettl14n6methyladenosinemethyltransferase

	solutionstructureofthernarecognitiondomainofmettl3mettl14n6methyladenosinemethyltransferase
	Huang Jinbo 2; Dong Xu 1; Gong Zhou 1; Qin Lingyun 1; Yang Shuai 1; Zhu Yueling 1; Wang Xiang 2; Zhang Delin 2; Zou Tingting 2; Yin Ping 2
刊名	蛋白质与细胞英文版
	2019
卷号	010 期号:004 页码:272
ISSN号	1674-800X
英文摘要	N^6-methyladenosine(m6A),a ubiquitous RNA modification,is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between the methyltransferase domains(MTDs)of METTL3 and METTL14 has been previously determined.However,the MTDs alone possess no enzymatic activity.Here we present the solution structure for the zinc finger domain(ZFD)of METTL3,the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14.We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3'consensus sequence,but does not to one without.The ZFD thus serves as the target recognition domain,a structural feature previously shown for DNA methyltransferases,and cooperates with the MTDs of METTL3-METTL14 for catalysis.However,the interaction between the ZFD and the specific RNA is extremely weak,with the binding affinity at several hundred micromolar under physiological conditions.The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel P-sheet.Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface.As a division of labor,the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues fromβ-sheet and zinc finger 2.Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded,which may permit the cooperation between the two domains during catalysis.Together,the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA m6A modification.
语种	英语
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/15367]
专题	中国科学院武汉物理与数学研究所
作者单位	1.中国科学院武汉物理与数学研究所 2.huazhong agricultural university
推荐引用方式 GB/T 7714	Huang Jinbo,Dong Xu,Gong Zhou,et al. solutionstructureofthernarecognitiondomainofmettl3mettl14n6methyladenosinemethyltransferase[J]. 蛋白质与细胞英文版,2019,010(004):272.
APA	Huang Jinbo.,Dong Xu.,Gong Zhou.,Qin Lingyun.,Yang Shuai.,...&Tang Chun.(2019).solutionstructureofthernarecognitiondomainofmettl3mettl14n6methyladenosinemethyltransferase.蛋白质与细胞英文版,010(004),272.
MLA	Huang Jinbo,et al."solutionstructureofthernarecognitiondomainofmettl3mettl14n6methyladenosinemethyltransferase".蛋白质与细胞英文版 010.004(2019):272.