Dual-Functional Titanium(IV) Immobilized Metal Affinity Chromatography Approach for Enabling Large-Scale Profiling of Protein Mannose-6-Phosphate Glycosylation and Revealing Its Predominant Substrates

doi:10.1021/acs.analchem.9b01698

	Dual-Functional Titanium(IV) Immobilized Metal Affinity Chromatography Approach for Enabling Large-Scale Profiling of Protein Mannose-6-Phosphate Glycosylation and Revealing Its Predominant Substrates
	Huang, Junfeng 2; Dong, Jing 1; Shi, Xudong 3; Chen, Zhengwei 4; Cui, Yusi 4; Liu, Xiaoyan 1; Ye, Mingliang 1; Li, Lingjun 2,4,5
刊名	ANALYTICAL CHEMISTRY
	2019-09-17
卷号	91 期号:18 页码:11589-11597
ISSN号	0003-2700
DOI	10.1021/acs.analchem.9b01698
通讯作者	Ye, Mingliang(mingliang@dicp.ac.cn) ; Li, Lingjun(lingjun.li@wisc.edu)
英文摘要	Mannose-6-phosphate (M6P) glycosylation is an important post-translational modification (PTM) and plays a crucial role in transferring lysosomal hydrolases to lysosome, and is involved in several other biological processes. Aberrant M6P modifications have been implicated in lysosomal storage diseases and numerous other disorders including Alzheimer's disease and cancer. Research on profiling of intact M6P glycopeptides remains challenging due to its extremely low stoichiometry. Here we propose a dual-mode affinity approach to enrich M6P glycopeptides by dual-functional titanium(IV) immobilized metal affinity chromatography [Ti(IV)-IMAC] materials. In combination with state-of-the-art mass spectrometry and database search engine, we profiled 237 intact M6P glycopeptides corresponding to 81 M6P glycoproteins in five types of tissues in mouse, representing the first large-scale profiling of M6P glycosylation in mouse samples. The analysis of M6P glycoforms revealed the predominant glycan substrates of this PTM. Gene ontology analysis showed that overrepresented M6P glycoproteins were lysosomal-associated proteins. However, there were still substantial M6P glycoproteins that possessed different subcellular locations and molecular functions. Deep mining of their roles implicated in lysosomal and nonlysosomal function can provide new insights into functional roles of this important yet poorly studied modification.
资助项目	National Key R&D Program of China[2016YFA0501402] ; National Natural Science Foundation of China[21535008] ; National Natural Science Foundation of China[21525524] ; National Institutes of Health[U01CA231081] ; National Institutes of Health[RF1AG052324] ; National Institutes of Health[ROI DK071801] ; NIH Shared Instrument Grant[NIH-NCRR S10RR029531] ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; Wisconsin Alumni Research Foundation ; University of Wisconsin-Madison School of Pharmacy
WOS关键词	LYSOSOMAL ACID LIPASE ; MANNOSE 6-PHOSPHATE ; PHOSPHOPEPTIDE ENRICHMENT ; IDENTIFICATION ; PHOSPHORYLATION ; GLYCOPROTEOMICS ; LIVER ; PROTEOMICS ; RECEPTOR ; ENZYMES
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000487156900017
资助机构	National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institutes of Health ; National Institutes of Health ; NIH Shared Instrument Grant ; NIH Shared Instrument Grant ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; Wisconsin Alumni Research Foundation ; Wisconsin Alumni Research Foundation ; University of Wisconsin-Madison School of Pharmacy ; University of Wisconsin-Madison School of Pharmacy ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institutes of Health ; National Institutes of Health ; NIH Shared Instrument Grant ; NIH Shared Instrument Grant ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; Wisconsin Alumni Research Foundation ; Wisconsin Alumni Research Foundation ; University of Wisconsin-Madison School of Pharmacy ; University of Wisconsin-Madison School of Pharmacy ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institutes of Health ; National Institutes of Health ; NIH Shared Instrument Grant ; NIH Shared Instrument Grant ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; Wisconsin Alumni Research Foundation ; Wisconsin Alumni Research Foundation ; University of Wisconsin-Madison School of Pharmacy ; University of Wisconsin-Madison School of Pharmacy ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Institutes of Health ; National Institutes of Health ; NIH Shared Instrument Grant ; NIH Shared Instrument Grant ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; University of Wisconsin Madison, Office of the Vice Chancellor for Research and Graduate Education ; Wisconsin Alumni Research Foundation ; Wisconsin Alumni Research Foundation ; University of Wisconsin-Madison School of Pharmacy ; University of Wisconsin-Madison School of Pharmacy
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/172771]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Ye, Mingliang; Li, Lingjun
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, Natl Chromatog R&A Ctr, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China 2.Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA 3.Univ Wisconsin, Dept Surg, Madison, WI 53705 USA 4.Univ Wisconsin, Dept Chem, Madison, WI 53705 USA 5.Tianjin Univ, Sch Life Sci, Tianjin 300072, Peoples R China
推荐引用方式 GB/T 7714	Huang, Junfeng,Dong, Jing,Shi, Xudong,et al. Dual-Functional Titanium(IV) Immobilized Metal Affinity Chromatography Approach for Enabling Large-Scale Profiling of Protein Mannose-6-Phosphate Glycosylation and Revealing Its Predominant Substrates[J]. ANALYTICAL CHEMISTRY,2019,91(18):11589-11597.
APA	Huang, Junfeng.,Dong, Jing.,Shi, Xudong.,Chen, Zhengwei.,Cui, Yusi.,...&Li, Lingjun.(2019).Dual-Functional Titanium(IV) Immobilized Metal Affinity Chromatography Approach for Enabling Large-Scale Profiling of Protein Mannose-6-Phosphate Glycosylation and Revealing Its Predominant Substrates.ANALYTICAL CHEMISTRY,91(18),11589-11597.
MLA	Huang, Junfeng,et al."Dual-Functional Titanium(IV) Immobilized Metal Affinity Chromatography Approach for Enabling Large-Scale Profiling of Protein Mannose-6-Phosphate Glycosylation and Revealing Its Predominant Substrates".ANALYTICAL CHEMISTRY 91.18(2019):11589-11597.