色谱与质谱联用技术在蛋白质翻译后修饰研究中的进展及应用
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摘要
蛋白质翻译后修饰是调控各种细胞信号通路和细胞命运最为关键的分子机制之一。在分子水平上,蛋白质翻译后修饰的"写入"、"擦除"和"识别"是实现其动态调控功能的核心过程,均属于生物分析化学的研究范畴。基于液相色谱与生物质谱联用的蛋白质组学技术经历了近十年的高速发展,已成为系统水平上表征各种蛋白质翻译后修饰的标准方法。本文综述了蛋白质翻译后修饰分析相关的关键技术和方法进展,主要包括:各种翻译后修饰蛋白质和多肽的富集方法、基于高效液相色谱的多维分离方法和各种生物质谱鉴定方法,并重点阐述了近年来的新的发展方向。基于相关技术的快速发展和大规模鉴定数据的产生,本文重点介绍了5种具有重要生物学功能的蛋白质翻译后修饰,包括:磷酸化、糖基化、泛素化、乙酰化和甲基化。生物分析化学领域的方法和技术创新必将进一步促进对蛋白质翻译后修饰的系统水平研究的发展。
Post translational modifications( PTMs) are the most important molecular processes for regulating various signaling pathways and determining specific cell fate. At molecular level,PTMs related "writing","erasing"and"reading"processes are the most critical processes for realizing their dynamic regulation and all belong to the research areas of biological analytical chemistry. LC-MS-based proteomics have been extensively developed in the past decade and become the standard approach for characterizing different PTMs on a global scale. Here,we will summarize key innovation for developing PTMs enrichment strategies,high-performance liquid chromatography-based fractionation approaches,mass spectrometry detection methods and some new research directions. With recent great effort from the proteomics society for developing highly efficient enriching methods and building comprehensive resources,we will specifically focus our discussion on five major types of PTMs,including phosphorylation,glycosylation,ubiquitination,acetylation and methylation.We expect the methodology and technology innovation in bioanalytical chemistry field will greatly facilitate the protein PTMs research at system level.
Post translational modifications( PTMs) are the most important molecular processes for regulating various signaling pathways and determining specific cell fate. At molecular level,PTMs related "writing","erasing"and"reading"processes are the most critical processes for realizing their dynamic regulation and all belong to the research areas of biological analytical chemistry. LC-MS-based proteomics have been extensively developed in the past decade and become the standard approach for characterizing different PTMs on a global scale. Here,we will summarize key innovation for developing PTMs enrichment strategies,high-performance liquid chromatography-based fractionation approaches,mass spectrometry detection methods and some new research directions. With recent great effort from the proteomics society for developing highly efficient enriching methods and building comprehensive resources,we will specifically focus our discussion on five major types of PTMs,including phosphorylation,glycosylation,ubiquitination,acetylation and methylation.We expect the methodology and technology innovation in bioanalytical chemistry field will greatly facilitate the protein PTMs research at system level.
引文
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2 Witze E S,Old W M,Resing K A,Ahn N G.Nat.Methods,2007,4:798-806
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28 Zhang H,Li X J,Martin D B,Aebersold R.Nat.Biotechnol.,2003,21:660-666
29 Zhang Y,Yu M,Zhang C,Ma W,Zhang Y,Wang C,Lu H.Anal.Chem.,2014,86(15):7920-7924
30 Peng J,Schwartz D,Elias J E,Thoreen C C,Cheng D,Marsischky G,Roelofs J,Finley D,Gygi S P.Nat.Biotech.,2003,21:921-926
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32 Udeshi N D,Mertins P,Svinkina T,Carr SA.Nat.Protocols,2013,8:1950-1960
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34 Choudhary C,Kumar C,Gnad F,Nielsen M L,Rehman M,Walther T C,Olsen J V,Mann M.Science,2009,325:834-840
35 Boisvert F M,CtéJ,Boulanger M C,Richard S.Mol.Cell.Proteomics,2003,2:1319-1330
36 Seet B T,Dikic I,Zhou M M,Pawson T.Nature Reviews Mol.Cell.Biol.,2006,7:473-483
37 Machida K,Thompson C M,Dierck K,Jablonowski K,Karkkainen S,Liu B,Zhang H,Nash P D,Newman D K,Nollau P,Pawson T,Renkema G H,Saksela K,Schiller M R,Shin D G,Mayer B J.Mol.Cell,2007,26:899-915
38 Chen C,Nott T J,Jin J,Pawson T.Nat.Rev.Mol.Cell.Biol.,2011,12:629-642
39 Moore K E,Carlson S M,Camp N D,Cheung P,James R G,Chua K F,Wolf-Yadlin A,Gozani O.Mol.Cell,2013,50:444-456
40 Mertins P,Qiao J W,Patel J,Udeshi N D,Clauser K R,Mani D R,Burgess M W,Gillette M A,Jaffe J D,Carr S A.Nat.Methods,2013,10:634-637
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42 Link A J,Eng J,Schieltz D M,Carmack E,Mize G J,Morris D R,Garvik B M,Yates J R.Nat.Biotechnol.,1999,17:676-682
43 Motoyama A,Yates J R,3rd.Anal.Chem.,2008,80:7187-7193
44 Gilar M,Olivova P,Daly A E,Gebler J C.Anal.Chem.,2005,77:6426-6434
45 Boersema P J,Mohammed S,Heck A J.Anal.Bioanal.Chem.,2008,391:151-159
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47 Han G,Ye M,Zhou H,Jiang X,Feng S,Jiang X,Tian R,Wan D,Zou H,Gu J.Proteomics,2008,8:1346-1361
48 Wisniewski J R,Nagaraj N,Zougman A,Gnad F,Mann M.J.Proteome Res.,2010,9:3280-3289
49 Song C X,Ye M L,Han G H,Jiang X N,Wang F J,Yu Z Y,Zou H.Anal.Chem.,2010,82(1):53-56
50 Gilar M,Olivova P,Daly A E,Gebler J C.J.Sep.Sci.,2005,28:1694-1703
51 Kim M S,Pinto S M,Getnet D,Nirujogi R S,Manda S S,Chaerkady R.Nature,2014,509:575-581
52 Ficarro S B,Zhang Y,Carrasco-Alfonso M J,Garg B,Adelmant G,Webber J T.Mol.Cell.Proteomics,2011,10:O111 011064
53 Boersema P J,Mohammed S,Heck A J R.J.Mass Spec.,2009,44:861-878
54 Villen J,Beausoleil S A,Gygi S P.Proteomics,2008,8:4444-4452
55 Schroeder M J,Shabanowitz J,Schwartz J C,Hunt D F,Coon J J.Anal.Chem.,2004,76(13):3590-3598
56 Olsen J V,Macek B,Lange O,Makarov A,Horning S,Mann M.Nat.Methods,2007,4:709-712
57 Jedrychowski M P,Huttlin E L,Haas W,Sowa M E,Rad R,Gygi S P.Mol.Cell.Proteomics,2011,10:M111 009910
58 Syrstad E A,Turecek F.J.Am.Soc.Mass Spec.,2005,16:208-224
59 Chi A,Huttenhower C,Geer L Y,Coon J J,Syka J E P,Bai D L.Proc.Natl.Acad.Sci.U.S.A.,2007,104:2193-2198
60 Phanstiel D H,Brumbaugh J,Wenger C D,Tian S,Probasco M D,Bailey D J.Nat.Methods,2011,8:821-827
61 Zhu Z,Su X,Clark D F,Go E P,Desaire H.Anal.Chem.,2013,85:8403-8411
62 Frese C K,Zhou H,Taus T,Altelaar A F M,Mechter K,Heck A J R.J.Proteome Res.,2013,12:1520-1525
2 Witze E S,Old W M,Resing K A,Ahn N G.Nat.Methods,2007,4:798-806
3 Choudhary C,Mann M.Nat.Rev.Mol.Cell.Biol.,2010,11:427-439
4 Altelaar A F,Munoz J,Heck A J.Nat.Rev.Genet.,2013,14:35-48
5 Nilsson C L.Anal.Chem.,2012,84:735-746
6 Wang F,Song C,Cheng K,Jiang X,Ye M,Zou H.Anal.Chem.,2011,83:8078-8085
7 Sharma K,D'Souza R C,Tyanova S,Schaab C,Wisniewski J R,Cox J,Mann M.Cell Reports,2014,8:1583-1594
8 Udeshi N D,Svinkina T,Mertins P,Kuhn E,Mani D R,Qiao J W,Carr S A.Mol.Cell.Proteomics,2013,12:825-831
9 Lundby A,Lage K,Weinert B T,Bekker-Jensen D B,Secher A,Skovgaard T,Kelstrup C D,Dmytriyev A,Choudhary C,Lundby C,Olsen J V.Cell Reports,2012,2:419-431
10 Guo A,Gu H,Zhou J,Mulhern D,Wang Y,Lee K A,Yang V,Aguiar M,Kornhauser J,Jia X,Ren J,Beausolei S A,Silva J C,Vemulapalli V,Bedford M T,Comb M J.Mol.Cell.Proteomics,2014,13:372-387
11 Zielinska D F,Gnad F,Wisniewski J R,Mann M.Cell,2010,141:897-907
12 Olsen J V,Blagoev B,Gnad F,Macek B,Kumar C,Mortensen P,Mann M.Cell,2006,127:635-648
13 Sugiyama N,Masuda T,Shinoda K,Nakamura A,Tomita M,Ishihama Y.Mol.Cell.Proteomics,2007,6:1103-1109
14 Ficarro S B,Parikh J R,Blank N C,Marto J A.Anal.Chem.,2008,80:4606-4613
15 Larsen M R,Thingholm T E,Jensen O N,Roepstorff P,Jrgensen T J D.Mol.Cell.Proteomics,2005,4:873-886
16 Bodenmiller B,Mueller L N,Mueller M,Domon B,Aebersold R.Nat.Methods,2007,4:231-237
17 Wu J,Shakey Q,Liu W,Schuller A,Follettie M T.J.Proteome Res.,2007,6:4684-4689
18 Villen J,Gygi S P.Nat.Protocols,2008,3:1630-1638
19 Zhou H,Ye M,Dong J,Corradini E,Cristobal A,Heck A J,Zou H F,Mohammed S.Nat.Protocols,2013,8:461-480
20 Feng S,Ye M L,Zhou H J,Jiang X G,Jiang X N,Zou H F,Gong B.Mol.Cell.Proteomics,2007,6:1656-1665
21 Thingholm T E,Jensen O N,Robinson P J,Larsen M R.Mol.Cell.Proteomics,2008,7:661-671
22 Zhou H,Ye M,Dong J,Han G,Jiang X,Wu R,Zou H F.J.Proteome Res.,2008,7:3957-3967
23 Hunter T,Sefton B M.Proc.Natl.Acad.Sci.U.S.A.,1980,77:1311-1315
24 Rikova K,Guo A,Zeng Q,Possemato A,Yu J,Haack H.Cell,2007,131:1190-1203
25 Jorgensen C,Sherman A,Chen G I,Pasculescu A,Poliakov A,Hsiung M,Larsen,B,Wilkinson D G,Linding R,Pawson T.Science,2009,326:1502-1509
26 Tian R,Wang H,Gish G D,Petsalaki E,Pasculescu A,Shi Y,Mollenauerd M,Bagshawa R D,Yoseff N,Huntere T,Gingrasa A C,Weissd A,Pawsona T.Proc.Natl.Acad.Sci.U.S.A.,2015,112:E1594-E1603
27 Kaji H,Saito H,Yamauchi Y,Shinkawa T,Taoka M,Hirabayashi J,Kasai K,Takahashi N,Isobel T.Nat.Biotechnol.,2003,21:667-672
28 Zhang H,Li X J,Martin D B,Aebersold R.Nat.Biotechnol.,2003,21:660-666
29 Zhang Y,Yu M,Zhang C,Ma W,Zhang Y,Wang C,Lu H.Anal.Chem.,2014,86(15):7920-7924
30 Peng J,Schwartz D,Elias J E,Thoreen C C,Cheng D,Marsischky G,Roelofs J,Finley D,Gygi S P.Nat.Biotech.,2003,21:921-926
31 Kim W,Bennett E J,Huttlin E L,Guo A,Li J,Possemato A,Sowa M,Rad R,Rush J,Comb M J,Harper J W,Gygi S P.Mol.Cell,2011,44:325-340
32 Udeshi N D,Mertins P,Svinkina T,Carr SA.Nat.Protocols,2013,8:1950-1960
33 Kim S C,Sprung R,Chen Y,Xu Y,Ball H,Pei J,Cheng T,Kho Y,Xiao Hao,Lin X,Grishin N V,White M,Yang X J,Zhao Y.Mol.Cell,2006,23:607-618
34 Choudhary C,Kumar C,Gnad F,Nielsen M L,Rehman M,Walther T C,Olsen J V,Mann M.Science,2009,325:834-840
35 Boisvert F M,CtéJ,Boulanger M C,Richard S.Mol.Cell.Proteomics,2003,2:1319-1330
36 Seet B T,Dikic I,Zhou M M,Pawson T.Nature Reviews Mol.Cell.Biol.,2006,7:473-483
37 Machida K,Thompson C M,Dierck K,Jablonowski K,Karkkainen S,Liu B,Zhang H,Nash P D,Newman D K,Nollau P,Pawson T,Renkema G H,Saksela K,Schiller M R,Shin D G,Mayer B J.Mol.Cell,2007,26:899-915
38 Chen C,Nott T J,Jin J,Pawson T.Nat.Rev.Mol.Cell.Biol.,2011,12:629-642
39 Moore K E,Carlson S M,Camp N D,Cheung P,James R G,Chua K F,Wolf-Yadlin A,Gozani O.Mol.Cell,2013,50:444-456
40 Mertins P,Qiao J W,Patel J,Udeshi N D,Clauser K R,Mani D R,Burgess M W,Gillette M A,Jaffe J D,Carr S A.Nat.Methods,2013,10:634-637
41 Swaney D L,Beltrao P,Starita L,Guo A,Rush J,Fields S,Krogan N J,Villén J.Nat.Methods,2013,10:676-682
42 Link A J,Eng J,Schieltz D M,Carmack E,Mize G J,Morris D R,Garvik B M,Yates J R.Nat.Biotechnol.,1999,17:676-682
43 Motoyama A,Yates J R,3rd.Anal.Chem.,2008,80:7187-7193
44 Gilar M,Olivova P,Daly A E,Gebler J C.Anal.Chem.,2005,77:6426-6434
45 Boersema P J,Mohammed S,Heck A J.Anal.Bioanal.Chem.,2008,391:151-159
46 Huttlin E L,Jedrychowski M P,Elias J E,Goswami T,Rad R,Beausoleil S A,Villén J,Haas W,Sowa M E,Gygi S P.Cell,2010,143:1174-1189
47 Han G,Ye M,Zhou H,Jiang X,Feng S,Jiang X,Tian R,Wan D,Zou H,Gu J.Proteomics,2008,8:1346-1361
48 Wisniewski J R,Nagaraj N,Zougman A,Gnad F,Mann M.J.Proteome Res.,2010,9:3280-3289
49 Song C X,Ye M L,Han G H,Jiang X N,Wang F J,Yu Z Y,Zou H.Anal.Chem.,2010,82(1):53-56
50 Gilar M,Olivova P,Daly A E,Gebler J C.J.Sep.Sci.,2005,28:1694-1703
51 Kim M S,Pinto S M,Getnet D,Nirujogi R S,Manda S S,Chaerkady R.Nature,2014,509:575-581
52 Ficarro S B,Zhang Y,Carrasco-Alfonso M J,Garg B,Adelmant G,Webber J T.Mol.Cell.Proteomics,2011,10:O111 011064
53 Boersema P J,Mohammed S,Heck A J R.J.Mass Spec.,2009,44:861-878
54 Villen J,Beausoleil S A,Gygi S P.Proteomics,2008,8:4444-4452
55 Schroeder M J,Shabanowitz J,Schwartz J C,Hunt D F,Coon J J.Anal.Chem.,2004,76(13):3590-3598
56 Olsen J V,Macek B,Lange O,Makarov A,Horning S,Mann M.Nat.Methods,2007,4:709-712
57 Jedrychowski M P,Huttlin E L,Haas W,Sowa M E,Rad R,Gygi S P.Mol.Cell.Proteomics,2011,10:M111 009910
58 Syrstad E A,Turecek F.J.Am.Soc.Mass Spec.,2005,16:208-224
59 Chi A,Huttenhower C,Geer L Y,Coon J J,Syka J E P,Bai D L.Proc.Natl.Acad.Sci.U.S.A.,2007,104:2193-2198
60 Phanstiel D H,Brumbaugh J,Wenger C D,Tian S,Probasco M D,Bailey D J.Nat.Methods,2011,8:821-827
61 Zhu Z,Su X,Clark D F,Go E P,Desaire H.Anal.Chem.,2013,85:8403-8411
62 Frese C K,Zhou H,Taus T,Altelaar A F M,Mechter K,Heck A J R.J.Proteome Res.,2013,12:1520-1525