Multiple Domains of GlcNAc-1-phosphotransferase Mediate Recognition of Lysosomal Enzymes

doi:10.1074/jbc.M116.714568

KMS > 生命科学与技术学院 > 特聘教授组 > James E. Rothman组

	Multiple Domains of GlcNAc-1-phosphotransferase Mediate Recognition of Lysosomal Enzymes
	van Meel, Eline 1,2; Lee, Wang-Sik 1; Liu, Lin 1; Qian, Yi1,3 ; Doray, Balraj 1; Kornfeld, Stuart 1
	2016-04-08
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN	0021-9258
卷号	291 期号:15 页码:8295-8307
发表状态	已发表
DOI	10.1074/jbc.M116.714568
摘要	The Golgi enzyme UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase), an (222) hexamer, mediates the initial step in the addition of the mannose 6-phosphate targeting signal on newly synthesized lysosomal enzymes. This tag serves to direct the lysosomal enzymes to lysosomes. A key property of GlcNAc-1-phosphotransferase is its unique ability to distinguish the 60 or so lysosomal enzymes from the numerous non-lysosomal glycoproteins with identical Asn-linked glycans. In this study, we demonstrate that the two Notch repeat modules and the DNA methyltransferase-associated protein interaction domain of the subunit are key components of this recognition process. Importantly, different combinations of these domains are involved in binding to individual lysosomal enzymes. This study also identifies the -binding site on the subunit and demonstrates that in the majority of instances the mannose 6-phosphate receptor homology domain of the subunit is required for optimal phosphorylation. These findings serve to explain how GlcNAc-1-phosphotransferase recognizes a large number of proteins that lack a common structural motif.
关键词	lysosomal glycoprotein lysosomal storage disease lysosome mannose 6-phosphate (Man-6-P) phosphorylation
收录类别	SCI ; EI
语种	英语
资助项目	National Institutes of Health[CA-008759]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000374056700044
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号	20161802339649
EI主题词	Bins ; Proteins
EI分类号	Storage:694.4 ; Organic Compounds:804.1
WOS关键词	MANNOSE 6-PHOSPHATE RECEPTOR ; SITE-DIRECTED MUTAGENESIS ; UDP-N-ACETYLGLUCOSAMINE ; CATHEPSIN-D ; MRH DOMAIN ; BETA-GLUCURONIDASE ; ALPHA-SUBUNIT ; PHOSPHORYLATION ; OLIGOSACCHARIDES ; GLYCOSYLATION
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1873
专题	生命科学与技术学院_特聘教授组_James E. Rothman组免疫化学研究所
通讯作者	Kornfeld, Stuart
作者单位	1.Washington Univ, Sch Med, Dept Internal Med, Campus Box 8125,660 South Euclid Ave, St Louis, MO 63110 USA 2.Leiden Univ, Leiden Inst Chem, Dept Med Biochem, POB 9502, NL-2300 RA Leiden, Netherlands 3.Shanghai Tech Univ, Shanghai Inst Adv Immunochem Studies, Bldg 6,99 Haike Rd, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	van Meel, Eline,Lee, Wang-Sik,Liu, Lin,et al. Multiple Domains of GlcNAc-1-phosphotransferase Mediate Recognition of Lysosomal Enzymes[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016,291(15):8295-8307.
APA	van Meel, Eline,Lee, Wang-Sik,Liu, Lin,Qian, Yi,Doray, Balraj,&Kornfeld, Stuart.(2016).Multiple Domains of GlcNAc-1-phosphotransferase Mediate Recognition of Lysosomal Enzymes.JOURNAL OF BIOLOGICAL CHEMISTRY,291(15),8295-8307.
MLA	van Meel, Eline,et al."Multiple Domains of GlcNAc-1-phosphotransferase Mediate Recognition of Lysosomal Enzymes".JOURNAL OF BIOLOGICAL CHEMISTRY 291.15(2016):8295-8307.