A tandem mass spectrometer for improved transmission and analysis of large macromolecular assemblies

Analytical Chemistry
Frank SobottCarol V Robinson

Abstract

We report the design and first applications of a tandem mass spectrometer (a quadrupole time-of-flight mass spectrometer) optimized for the transmission and analysis of large macromolecular assemblies. Careful control of the pressure gradient in the different pumping stages of the instrument has been found to be essential for the detection of macromolecular particles. Such assemblies are, however, difficult to analyze by tandem-MS approaches, because they give rise to signals above m/z 3,000-4,000, the limit for commercial quadrupoles. By reducing the frequency of the quadrupole to 300 kHz and using it as a narrow-band mass filter, we show that it is possible to isolate ions from a single peak at m/z 22,000 in a window as narrow as 22 m/z units. Using cesium iodide cluster signals, we show that the mass range in the time-of-flight (TOF) analyzer extends beyond m/z 90,000, in theory to more than m/z 150,000. We also demonstrate that the resolution of the instrument is greater than 3,000 at m/z 44,500. Tandem-MS capabilities are illustrated by separating components from heterooligomeric assemblies formed between tetrameric transthyretin, thyroxine, retinol-binding protein, and retinol. Isolation of a single charge state at m/z 5,...Continue Reading

References

Feb 27, 1999·Current Opinion in Structural Biology·A A Rostom, C V Robinson
Nov 5, 1999·Protein Science : a Publication of the Protein Society·E W ChungC V Robinson
May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·A A RostomC V Robinson
May 18, 2000·Analytical Chemistry·A ShevchenkoK G Standing
Jul 11, 2001·Journal of the American Society for Mass Spectrometry·B B SchneiderD D Chen

❮ Previous
Next ❯

Citations

Apr 8, 2011·Journal of the American Society for Mass Spectrometry·Jiangjiang Liu, Lars Konermann
May 26, 2005·Journal of the American Society for Mass Spectrometry·Joseph A LooIgor V Chernushevich
Jun 29, 2007·Journal of the American Society for Mass Spectrometry·Greg M WaittJon D Williams
Jan 15, 2008·Journal of the American Society for Mass Spectrometry·Vicki H WysockiRichard L Beardsley
Jul 5, 2008·Journal of the American Society for Mass Spectrometry·Vicki H WysockiAnne E Blackwell
Jan 26, 2010·Journal of the American Society for Mass Spectrometry·Claudia BichRenato Zenobi
Feb 2, 2010·Journal of the American Society for Mass Spectrometry·Esther van Duijn
Feb 2, 2010·Journal of the American Society for Mass Spectrometry·Michal Sharon
Dec 23, 2003·Journal of Molecular Biology·Lars F WestbladeStephen J W Busby
Sep 5, 2006·Molecular Cell·Cara K VaughanLaurence H Pearl
Dec 31, 2002·Current Opinion in Structural Biology·Frank Sobott, Carol V Robinson
Dec 18, 2002·Journal of the American Society for Mass Spectrometry·Peter B O'ConnorWilliam E Earle
Jul 7, 2011·Analytical Chemistry·Jeonghoon Lee, Peter T A Reilly
Jan 25, 2011·Nature Chemistry·Charlotte UetrechtAlbert J R Heck
Sep 20, 2006·Nature Chemical Biology·Julie A Leary
Jul 7, 2009·Nature Methods·Nelson P BarreraCarol V Robinson
Oct 16, 2012·Nature Methods·Rebecca J RoseAlbert J R Heck
Oct 15, 2013·Nature Methods·Jonathan T S HopperCarol V Robinson
Apr 5, 2007·Nature Protocols·Helena Hernández, Carol V Robinson
Jul 5, 2008·Nature Protocols·Brandon T RuotoloCarol V Robinson
Mar 9, 2013·Nature Protocols·Arthur LaganowskyCarol V Robinson
Oct 12, 2010·Nature Structural & Molecular Biology·Liwei WangHao Wu
May 10, 2011·Nature Structural & Molecular Biology·Yuan TianDinshaw J Patel
Jan 17, 2012·Nature Structural & Molecular Biology·Hélène MaletHelen R Saibil
Jan 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ian J MacRaeJennifer A Doudna
Jul 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Charlotte UetrechtAlbert J R Heck
Jul 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Min ZhouCarol V Robinson
Jun 17, 2008·Science·Nelson P BarreraCarol V Robinson
Mar 3, 2007·Annual Review of Biochemistry·Michal Sharon, Carol V Robinson
Oct 4, 2006·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Satoko Akashi
Jul 14, 2009·PloS One·Saroj VelamakanniHendrik W van Veen
Sep 29, 2009·PloS One·Helena HernándezCarol V Robinson
Feb 11, 2014·Nature Methods·Argyris PolitisRuedi Aebersold
Feb 7, 2014·Journal of the American Society for Mass Spectrometry·Hélène LavanantCarlos Afonso
Apr 8, 2014·Nature Chemical Biology·Indran MathavanKonstantinos Beis
Aug 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·J Andrew AquilinaCarol V Robinson
Jan 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Valerie E PyePaul S Freemont

❮ Previous
Next ❯

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.