Large-Scale Differentiation and Site Specific Discrimination of Hydroxyproline Isomers by Electron Transfer/Higher-Energy Collision Dissociation (EThcD) Mass Spectrometry
文献类型：期刊论文
| 作者 | Ma, Fengfei2; Sun, Ruixiang1; Tremmel, Daniel M.4; Sacket, Sara Dutton4; Odorico, Jon4; Li, Lingjun2,3 |
| 刊名 | ANALYTICAL CHEMISTRY
 |
| 出版日期 | 2018-05-01 |
| 卷号 | 90期号:9页码:5857-5864 |
| ISSN号 | 0003-2700 |
| DOI | 10.1021/acs.analchem8b00413 |
| 英文摘要 | 3- and 4-Hydroxyprolines (HyP) are regioisomers that play different roles in various species and organs. Despite their distinct functions inside cells, they are generally considered indistinguishable using mass spectrometry due to their identical masses. Here, we demonstrate, for the first time, that characteristic w ions can be produced by electron-transfer/higher energy collision dissociation (EThcD) dual fragmentation technique to confidently discriminate 3-HyP/4-HyP isomers. An integrated and high throughput strategy was developed which combined online LC separation with EThcD for large-scale differentiation of 3-HyP/4-HyP in complex samples. An automated algorithm was developed for charge state dependent characterization of 3-HyP/4-HyP isomers. Using this combined discrimination approach, we identified 108 3-HyP sites and 530 4-HyP sites from decellularized pancreas, allowing more than 5-fold increase of both 3-HyP and 4-HyP identifications compared to previous reports. This approach outperformed ETD and HCD in the analysis of HyP-containing peptides with unique capacity to generate w ions for HyP discrimination, improved fragmentation of precursor ions, as well as unambiguous localization of modifications. A high content of 3-HyP was observed in the C-terminal (GPP)(n) domain of human CO1A1, which was previously only identified in vertebrate fibrillar collagens from tendon. Unexpectedly, some unusual HyP sites at Xaa position in Gly-HyP-Ala, Gly-HyP-Val, Gly-HyP-Gln, Gly-HyP-Ser, and Gly-HyP-Arg were also confirmed to be 3-hydroxylated, whose functions and enzymes are yet to be discovered. Overall, this novel discrimination strategy can be readily implemented into de novo sequencing or other proteomic search engines. |
| 资助项目 | National Institutes of Health[R21AI126419] ; National Institutes of Health[R01DK071801] ; National Institutes of Health[R01AG052324] ; National Institutes of Health[P41GM108538] ; NIH[NIH-NCRR S10RR029531] ; Office of the Vice Chancellor for Research and Graduate Education at the University of Wisconsin-Madison ; Wisconsin Alumni Research Foundation ; University of Wisconsin-Madison School of Pharmacy |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000431464400047 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.204/handle/2XEOYT63/5319]  |
| 专题 | 中国科学院计算技术研究所期刊论文_英文 |
| 通讯作者 | Li, Lingjun |
| 作者单位 | 1.Chinese Acad Sci, Inst Comp Technol, Beijing 100190, Peoples R China 2.Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA 3.Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA 4.Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Div Transplantat, Madison, WI 53705 USA |
| 推荐引用方式 GB/T 7714 | Ma, Fengfei,Sun, Ruixiang,Tremmel, Daniel M.,et al. Large-Scale Differentiation and Site Specific Discrimination of Hydroxyproline Isomers by Electron Transfer/Higher-Energy Collision Dissociation (EThcD) Mass Spectrometry[J]. ANALYTICAL CHEMISTRY,2018,90(9):5857-5864. |
| APA | Ma, Fengfei,Sun, Ruixiang,Tremmel, Daniel M.,Sacket, Sara Dutton,Odorico, Jon,&Li, Lingjun.(2018).Large-Scale Differentiation and Site Specific Discrimination of Hydroxyproline Isomers by Electron Transfer/Higher-Energy Collision Dissociation (EThcD) Mass Spectrometry.ANALYTICAL CHEMISTRY,90(9),5857-5864. |
| MLA | Ma, Fengfei,et al."Large-Scale Differentiation and Site Specific Discrimination of Hydroxyproline Isomers by Electron Transfer/Higher-Energy Collision Dissociation (EThcD) Mass Spectrometry".ANALYTICAL CHEMISTRY 90.9(2018):5857-5864. |
入库方式： OAI收割
来源：计算技术研究所
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