Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification

Nature Communications
Fan LiuAlbert J R Heck

Abstract

We describe optimized fragmentation schemes and data analysis strategies substantially enhancing the depth and accuracy in identifying protein cross-links using non-restricted whole proteome databases. These include a novel hybrid data acquisition strategy to sequence cross-links at both MS2 and MS3 level and a new algorithmic design XlinkX v2.0 for data analysis. As proof-of-concept we investigated proteome-wide protein interactions in E. coli and HeLa cell lysates, respectively, identifying 1,158 and 3,301 unique cross-links at ∼1% false discovery rate. These protein interaction repositories provide meaningful structural information on many endogenous macromolecular assemblies, as we showcase on several protein complexes involved in translation, protein folding and carbohydrate metabolism.

References

Mar 9, 2002·Science·F Ulrich Hartl, Manajit Hayer-Hartl
Aug 2, 2003·Journal of the American Society for Mass Spectrometry·Birgit SchillingMalin M Young
Apr 3, 2010·Molecular & Cellular Proteomics : MCP·Alexander LeitnerRuedi Aebersold
Dec 18, 2013·Molecular & Cellular Proteomics : MCP·Michael J TrnkaRobert J Chalkley
Sep 26, 2014·Molecular & Cellular Proteomics : MCP·Robyn M KaakeLan Huang
May 8, 2015·Nature Protocols·Lawrence A KelleyMichael J E Sternberg
Nov 1, 2016·The EMBO Journal·Philip LösslAlbert Jr Heck
Feb 1, 2014·Molecular & Cellular Proteomics : MCP·Michael J TrnkaRobert J Chalkley

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Citations

Jul 20, 2018·Molecular & Cellular Proteomics : MCP·Domenico FasciAlbert J R Heck
Sep 27, 2019·Molecular Systems Biology·Marta L MendesJuri Rappsilber
Oct 28, 2019·Journal of Biochemistry·Takumi Koshiba, Hidetaka Kosako
Dec 17, 2019·Molecular & Cellular Proteomics : MCP·Kumar YugandharHaiyuan Yu
Jul 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mikayla ShanafeltCraig Vierra
Jul 23, 2020·Molecular & Cellular Proteomics : MCP·Barbara SteigenbergerRichard A Scheltema
Oct 9, 2019·Chembiochem : a European Journal of Chemical Biology·Michael StadlmeierThomas Carell
Apr 26, 2020·Molecular & Cellular Proteomics : MCP·Andreas LindenHenning Urlaub
Feb 28, 2020·Genome Biology·Yan-Ru CuiJia Liu
Aug 25, 2020·Advanced Science·Pingdong TaoRichard A Lerner
Mar 27, 2019·Scientific Reports·Lucía Quintana-GallardoJosé María Valpuesta
Jul 10, 2020·Nucleic Acids Research·Krishnendu KhanPaul L Fox
May 10, 2018·Nucleic Acids Research·Lars KolbowskiJuri Rappsilber
Apr 3, 2020·Nature Reviews. Molecular Cell Biology·Isabell Bludau, Ruedi Aebersold
Jul 22, 2020·Nature Microbiology·Huib H RabouwFrank J M van Kuppeveld
Dec 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xingyu LiuMichael P Washburn
Jan 13, 2021·Molecular Systems Biology·Alicia L RichardsNevan J Krogan
Nov 19, 2020·Molecular & Cellular Proteomics : MCP·Congcong LuBenjamin A Garcia
Feb 12, 2021·Science Advances·Sarah A MosureDouglas J Kojetin
May 30, 2020·Molecular & Cellular Proteomics : MCP·Mark K AdamsMichael P Washburn
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Andreas LindenHenning Urlaub
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Mark K AdamsMichael P Washburn
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Barbara SteigenbergerRichard A Scheltema
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Kumar YugandharHaiyuan Yu
Feb 17, 2021·Analytical Chemistry·Jasjot SinghDominic Winter
Jan 15, 2020·Journal of the American Society for Mass Spectrometry·Andrew NorrisVicki H Wysocki
Mar 4, 2021·Mass Spectrometry Reviews·Jarne PauwelsKris Gevaert
Aug 24, 2020·Current Opinion in Chemical Biology·Adam Belsom, Juri Rappsilber
Nov 24, 2017·Current Opinion in Chemical Biology·Elizabeth A RowlandIleana M Cristea

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Methods Mentioned

BETA
protein folding
interaction mapping

Software Mentioned

MS2
XlinkX
Phyre2
Proteome Discoverer
- Spectrum Processor
XL
Sequest

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