Improved molecular weight-based processing of intact proteins for interrogation by quadrupole-enhanced FT MS/MS

Journal of Proteome Research
Yi DuNeil L Kelleher

Abstract

Complete coverage of protein primary structure is demonstrated for 37 yeast protein forms between 6 and 30 kDa in an improved platform for Top Down mass spectrometry (MS). Tandem mass spectrometry (MS/MS) for protein identification with 100% sequence coverage is achieved in a highly automated fashion with 15-300-fold less sample amounts than an initial report of a proteome fractionation approach employing preparative gel electrophoresis with an acid-labile surfactant to facilitate reversed phase separation in a second dimension. Using a quadrupole-enhanced Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICRMS) improves the dynamic range for protein detection by approximately 50-fold and MS/MS by approximately 30-fold. The technology development illustrated here typifies an accelerating effort to detect whole proteins in a more general and higher throughput fashion for improved biomarker identification and detection of diverse post-translational modifications. Capillary RPLC is used in both off-line and on-line modes, with one on-line LC/FTMS sample providing 25 observed protein forms from 11 to 22 kDa.

References

Jan 1, 1996·Analytical Chemistry·M Wilm, M Mann
Jan 1, 1996·Rapid Communications in Mass Spectrometry : RCM·M W SenkoA G Marshall
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·A ShevchenkoM Mann
Apr 15, 1997·Analytical Chemistry·G J OpiteckR J Anderegg
Jul 1, 1997·Analytical Chemistry·G J Opiteck, J W Jorgenson
Jul 15, 1999·Nature Biotechnology·A J LinkJ R Yates
Mar 5, 2002·Nature Biotechnology·Scott B FicarroForest M White
Apr 23, 2002·Rapid Communications in Mass Spectrometry : RCM·Magnus PalmbladPer Håkansson
May 2, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sang-Won LeeRichard D Smith
Jul 4, 2002·Molecular & Cellular Proteomics : MCP·Stephen M GómezJulian P Whitelegge
Jul 27, 2002·Analytical Chemistry·Fanyu MengNeil L Kelleher
Sep 26, 2002·Electrophoresis·Yufeng Shen, Richard D Smith
Nov 30, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Jonathan A KartyJames P Reilly
Nov 25, 2003·Analytical Chemistry·Gregory K TaylorNeil L Kelleher
Dec 13, 2003·Analytical Chemistry·Derek T McLachlin, Brian T Chait

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Citations

Jul 24, 2012·Amino Acids·Timothy S Collier, David Charles Muddiman
Oct 29, 2005·Journal of the American Society for Mass Spectrometry·Vlad ZabrouskovNeil L Kelleher
Nov 8, 2005·Journal of the American Society for Mass Spectrometry·Judith A JebanathirajahPeter B O'Connor
Sep 24, 2009·Journal of the American Society for Mass Spectrometry·Yihsuan S TsaiDavid R Goodlett
Sep 15, 2009·Journal of the American Society for Mass Spectrometry·Ji Eun LeeNeil L Kelleher
Sep 1, 2009·Bioanalysis·Marcus Macht
Jun 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Joshua J CoonDonald F Hunt
May 11, 2005·Protein Science : a Publication of the Protein Society·Yonghao YuJulie A Leary
Aug 23, 2006·Journal of Mass Spectrometry : JMS·Elena V RomanovaJonathan V Sweedler
Sep 23, 2010·Proteomics·Andrea Armirotti, Gianluca Damonte
Aug 31, 2013·Current Opinion in Chemical Biology·Dorothy R AhlfNeil L Kelleher
Feb 22, 2014·Biochemical and Biophysical Research Communications·Adam D CathermanNeil L Kelleher
Aug 19, 2015·Current Opinion in Neurobiology·Susumu TonegawaTomás J Ryan
Oct 22, 2016·Biological Psychiatry·Andrés Uribe-MariñoMathias V Schmidt
Jun 26, 2013·Current Opinion in Biotechnology·K M A GartlandY Akbarova
Oct 8, 2005·Expert Review of Proteomics·Yueju WangCheng S Lee
Jul 25, 2007·Chemical Reviews·Gert Lubec, Leila Afjehi-Sadat

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