X-ray spectroscopy meets native mass spectrometry: probing gas-phase protein complexes
Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu časopisecké články, přehledy
PubMed
40304431
PubMed Central
PMC12042735
DOI
10.1039/d5cp00604j
Knihovny.cz E-zdroje
- MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- hmotnostní spektrometrie * MeSH
- plyny * chemie MeSH
- proteiny * chemie MeSH
- rentgenové záření MeSH
- synchrotrony MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- plyny * MeSH
- proteiny * MeSH
Gas-phase activation and dissociation studies of biomolecules, proteins and their non-covalent complexes using X-rays hold great promise for revealing new insights into the structure and function of biological samples. This is due to the unique properties of X-ray molecular interactions, such as site-specific and rapid ionization. In this perspective, we report and discuss the promise of first proof-of-principle studies of X-ray-induced dissociation of native (structurally preserved) biological samples ranging from small 17 kDa monomeric proteins up to large 808 kDa non-covalent protein assemblies conducted at a synchrotron (PETRA III) and a free-electron laser (FLASH2). A commercially available quadrupole time-of-flight mass spectrometer (Q-Tof Ultima US, Micromass/Waters), modified for high-mass analysis by MS Vision, was further adapted for integration with the open ports at the corresponding beamlines. The protein complexes were transferred natively into the gas phase via nano-electrospray ionization and subsequently probed by extreme ultraviolet (FLASH2) or soft X-ray (PETRA III) radiation, in either their folded state or following collision-induced activation in the gas phase. Depending on the size of the biomolecule and the activation method, protein fragmentation, dissociation, or enhanced ionization were observed. Additionally, an extension of the setup by ion mobility is described, which can serve as a powerful tool for structural separation of biomolecules prior to X-ray probing. The first experimental results are discussed in the broader context of current and upcoming X-ray sources, highlighting their potential for advancing structural biology in the future.
Center for Free Electron Laser Science Deutsches Elektronen Synchrotron 22607 Hamburg Germany
Department of Physics and Astronomy Uppsala University Box 516 75120 Uppsala Sweden
Deutsches Elektronen Synchrotron DESY Notkestraße 85 22607 Hamburg Germany
European XFEL Holzkoppel 4 22869 Schenefeld Germany
Faculty 5 School of Life Sciences University of Siegen Adolf Reichwein Str 2a 57076 Siegen Germany
Institute of Microbiology Czech Academy of Sciences Videnska 1083 142 00 Prague Czech Republic
Institute of Physics University of Greifswald Felix Hausdorff Str 6 17489 Greifswald Germany
Leibniz Institute of Virology Martinistraße 52 20251 Hamburg Germany
Zobrazit více v PubMed
Leney A. C. Heck A. J. R. Native Mass Spectrometry: What is in the Name? J. Am. Soc. Mass Spectrom. 2017;28:5–13. PubMed PMC
Karas M. Bahr U. Dülcks T. Nano-electrospray ionization mass spectrometry: addressing analytical problems beyond routine. Fresenius’ J. Anal. Chem. 2000;366:669–676. PubMed
Lapthorn C. Pullen F. Chowdhry B. Z. Ion mobility spectrometry-mass spectrometry (IMS-MS) of small molecules: Separating and assigning structures to ions. Mass Spectrom. Rev. 2013;32:43–71. PubMed
Seo J. Hoffmann W. Warnke S. Bowers M. T. Pagel K. von Helden G. Retention of Native Protein Structures in the Absence of Solvent: A Coupled Ion Mobility and Spectroscopic Study. Angew. Chem., Int. Ed. 2016;55:14173–14176. PubMed PMC
Esser T. K. Böhning J. Önür A. Chinthapalli D. K. Eriksson L. Grabarics M. Fremdling P. Konijnenberg A. Makarov A. Botman A. Peter C. Benesch J. L. P. Robinson C. V. Gault J. Baker L. Bharat T. A. M. Rauschenbach S. Cryo-EM of soft-landed β-galactosidase: Gas-phase and native structures are remarkably similar. Sci. Adv. 2024;10:eadl4628. PubMed PMC
Zhurov K. O. Fornelli L. Wodrich M. D. Laskay Ü. A. Tsybin Y. O. Principles of electron capture and transfer dissociation mass spectrometry applied to peptide and protein structure analysis. Chem. Soc. Rev. 2013;42:5014–5030. PubMed
Snyder D. T. Harvey S. R. Wysocki V. H. Surface-induced Dissociation Mass Spectrometry as a Structural Biology Tool. Chem. Rev. 2022;122:7442–7487. PubMed PMC
Maitre P. Scuderi D. Corinti D. Chiavarino B. Crestoni M. E. Fornarini S. Applications of Infrared Multiple Photon Dissociation (IRMPD) to the Detection of Posttranslational Modifications. Chem. Rev. 2020;120:3261–3295. PubMed
Brodbelt J. S. Morrison L. J. Santos I. Ultraviolet Photodissociation Mass Spectrometry for Analysis of Biological Molecules. Chem. Rev. 2020;120:3328–3380. PubMed PMC
McLuckey S. A. Goeringer D. E. Slow Heating Methods in Tandem Mass Spectrometry. J. Mass Spectrom. 1997;32:461–474.
Egorov D. Schwob L. Lalande M. Hoekstra R. Schlathölter T. Near edge X-ray absorption mass spectrometry of gas phase proteins: the influence of protein size. Phys. Chem. Chem. Phys. 2016;18:26213–26223. PubMed
Egorov D. Bari S. Boll R. Dörner S. Deinert S. Techert S. Hoekstra R. Zamudio-Bayer V. Lindblad R. Bülow C. Timm M. von Issendorff B. Lau J. T. Schlathölter T. Near-Edge Soft X-ray Absorption Mass Spectrometry of Protonated Melittin. J. Am. Soc. Mass Spectrom. 2018;29:2138–2151. PubMed
Bari S. Egorov D. Jansen T. L. C. Boll R. Hoekstra R. Techert S. Zamudio-Bayer V. Bülow C. Lindblad R. Leistner G. Ławicki A. Hirsch K. Miedema P. S. von Issendorff B. Lau J. T. Schlathölter T. Soft X-ray Spectroscopy as a Probe for Gas-Phase Protein Structure: Electron Impact Ionization from Within. Chem. – Eur. J. 2018;24:7631–7636. PubMed PMC
Dörner S. Schwob L. Atak K. Schubert K. Boll R. Schlathölter T. Timm M. Bülow C. Zamudio-Bayer V. von Issendorff B. Lau J. T. Techert S. Bari S. Probing Structural Information of Gas-Phase Peptides by Near-Edge X-ray Absorption Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2021;32:670–684. PubMed
Zhou M. Lantz C. Brown K. A. Ge Y. Paša-Tolić L. Loo J. A. Lermyte F. Higher-order structural characterisation of native proteins and complexes by top-down mass spectrometry. Chem. Sci. 2020;11:12918–12936. PubMed PMC
Liu R. Xia S. Li H. Native top-down mass spectrometry for higher-order structural characterization of proteins and complexes. Mass Spectrom. Rev. 2023;42:1876–1926. PubMed
Uetrecht C. Rose R. J. van Duijn E. Lorenzen K. Heck A. J. R. Ion mobility mass spectrometry of proteins and protein assemblies. Chem. Soc. Rev. 2010;39:1633–1655. PubMed
Marklund E. G. Degiacomi M. T. Robinson C. V. Baldwin A. J. Benesch J. L. P. Collision Cross Sections for Structural Proteomics. Structure. 2015;23:791–799. PubMed
Narayanan S J J. Tripathi D. Verma P. Adhikary A. Dutta A. K. Secondary Electron Attachment-Induced Radiation Damage to Genetic Materials. ACS Omega. 2023;8:10669–10689. PubMed PMC
Viefhaus J. Scholz F. Deinert S. Glaser L. Ilchen M. Seltmann J. Walter P. Siewert F. The Variable Polarization XUV Beamline P04 at PETRA III: Optics, mechanics and their performance. Nucl. Instrum. Methods Phys. Res., Sect. A. 2013;710:151–154.
Faatz B. Braune M. Hensler O. Honkavaara K. Kammering R. Kuhlmann M. Ploenjes E. Roensch-Schulenburg J. Schneidmiller E. Schreiber S. Tiedtke K. Tischer M. Treusch R. Vogt M. Wurth W. Yurkov M. Zemella J. The FLASH Facility: Advanced Options for FLASH2 and Future Perspectives. Appl. Sci. 2017;7:1114.
Pogan R. Weiss V. U. Bond K. Dülfer J. Krisp C. Lyktey N. Müller-Guhl J. Zoratto S. Allmaier G. Jarrold M. F. Muñoz-Fontela C. Schlüter H. Uetrecht C. N-terminal VP1 Truncations Favor T = 1 Norovirus-Like Particles. Vaccines. 2021;9:8. PubMed PMC
Pogan R. Schneider C. Reimer R. Hansman G. Uetrecht C. Norovirus-like VP1 particles exhibit isolate dependent stability profiles. J. Phys.: Condens. Matter. 2018;30:064006. PubMed PMC
Uetrecht C. Versluis C. Watts N. R. Roos W. H. Wuite G. J. L. Wingfield P. T. Steven A. C. Heck A. J. R. High-resolution mass spectrometry of viral assemblies: Molecular composition and stability of dimorphic hepatitis B virus capsids. Proc. Natl. Acad. Sci. U. S. A. 2008;105:9216–9220. PubMed PMC
van den Heuvel R. H. H. van Duijn E. Mazon H. Synowsky S. A. Lorenzen K. Versluis C. Brouns S. J. J. Langridge D. van der Oost J. Hoyes J. Heck A. J. R. Improving the Performance of a Quadrupole Time-of-Flight Instrument for Macromolecular Mass Spectrometry. Anal. Chem. 2006;78:7473–7483. PubMed
Tiedtke K. Azima A. von Bargen N. Bittner L. Bonfigt S. Düsterer S. Faatz B. Frühling U. Gensch M. Gerth C. Guerassimova N. Hahn U. Hans T. Hesse M. Honkavaar K. Jastrow U. Juranic P. Kapitzki S. Keitel B. Kracht T. Kuhlmann M. Li W. B. Martins M. Núñez T. Plönjes E. Redlin H. Saldin E. L. Schneidmiller E. A. Schneider J. R. Schreiber S. Stojanovic N. Tavella F. Toleikis S. Treusch R. Weigelt H. Wellhöfer M. Wabnitz H. Yurkov M. V. Feldhaus J. The soft x-ray free-electron laser FLASH at DESY: beamlines, diagnostics and end-stations. New J. Phys. 2009;11:023029.
Rossbach J., in Synchrotron Light Sources and Free-Electron Lasers: Accelerator Physics, Instrumentation and Science Applications, ed. E. J. Jaeschke, S. Khan, J. R. Schneider and J. B. Hastings, Springer International Publishing, Cham, 2016, pp. 303–328
McCullough B. J. Kalapothakis J. Eastwood H. Kemper P. MacMillan D. Taylor K. Dorin J. Barran P. E. Development of an Ion Mobility Quadrupole Time of Flight Mass Spectrometer. Anal. Chem. 2008;80:6336–6344. PubMed
Kierspel T. Kadek A. Barran P. Bellina B. Bijedic A. Brodmerkel M. N. Commandeur J. Caleman C. Damjanović T. Dawod I. De Santis E. Lekkas A. Lorenzen K. López Morillo L. Mandl T. Marklund E. G. Papanastasiou D. Ramakers L. A. I. Schweikhard L. Simke F. Sinelnikova A. Smyrnakis A. Timneanu N. Uetrecht C. for the MS SPIDOC Consortium Coherent diffractive imaging of proteins and viral capsids: simulating MS SPIDOC. Anal. Bioanal. Chem. 2023;415:4209–4220. PubMed PMC
Caleman C. Ortiz C. Marklund E. Bultmark F. Gabrysch M. Parak F. G. Hajdu J. Klintenberg M. Tîmneanu N. Radiation damage in biological material: Electronic properties and electron impact ionization in urea. Europhys. Lett. 2009;85:18005.
Kopicki J.-D. Saikia A. Niebling S. Günther C. Anjanappa R. Garcia-Alai M. Springer S. Uetrecht C. Opening opportunities for Kd determination and screening of MHC peptide complexes. Commun. Biol. 2022;5:488. PubMed PMC
Beardsley R. L. Jones C. M. Galhena A. S. Wysocki V. H. Noncovalent Protein Tetramers and Pentamers with “n” Charges Yield Monomers with n/4 and n/5 Charges. Anal. Chem. 2009;81:1347–1356. PubMed PMC
Kadek A. Lorenzen K. Uetrecht C. for the MS SPIDOC consortium In a flash of light: X-ray free electron lasers meet native mass spectrometry. Drug Discovery Today:Technol. 2021;39:89–99. PubMed
Kaleta D. T. Jarrold M. F. Helix–Turn–Helix Motifs in Unsolvated Peptides. J. Am. Chem. Soc. 2003;125:7186–7187. PubMed
Theisen A. Yan B. Brown J. M. Morris M. Bellina B. Barran P. E. Use of Ultraviolet Photodissociation Coupled with Ion Mobility Mass Spectrometry To Determine Structure and Sequence from Drift Time Selected Peptides and Proteins. Anal. Chem. 2016;88:9964–9971. PubMed
Liu F. C. Ridgeway M. E. Winfred J. S. R. V. Polfer N. C. Lee J. Theisen A. Wootton C. A. Park M. A. Bleiholder C. Tandem-trapped ion mobility spectrometry/mass spectrometry coupled with ultraviolet photodissociation. Rapid Commun. Mass Spectrom. 2021;35:e9192. PubMed PMC
Santos-Fernandez M. Jeanne Dit Fouque K. Fernandez-Lima F. Integration of Trapped Ion Mobility Spectrometry and Ultraviolet Photodissociation in a Quadrupolar Ion Trap Mass Spectrometer. Anal. Chem. 2023;95:8417–8422. PubMed PMC
Bari S. Gonzalez-Magaña O. Reitsma G. Werner J. Schippers S. Hoekstra R. Schlathölter T. Photodissociation of protonated leucine-enkephalin in the VUV range of 8–40 eV. J. Chem. Phys. 2011;134:024314. PubMed
Bellina B. Brown J. M. Ujma J. Murray P. Giles K. Morris M. Compagnon I. Barran P. E. UV photodissociation of trapped ions following ion mobility separation in a Q-ToF mass spectrometer. Analyst. 2014;139:6348–6351. PubMed
Warnke S. Baldauf C. Bowers M. T. Pagel K. von Helden G. Photodissociation of Conformer-Selected Ubiquitin Ions Reveals Site-Specific Cis/Trans Isomerization of Proline Peptide Bonds. J. Am. Chem. Soc. 2014;136:10308–10314. PubMed
Simon A.-L. Chirot F. Choi C. M. Clavier C. Barbaire M. Maurelli J. Dagany X. MacAleese L. Dugourd P. Tandem ion mobility spectrometry coupled to laser excitation. Rev. Sci. Instrum. 2015;86:094101. PubMed
Daly S. MacAleese L. Dugourd P. Chirot F. Combining Structural Probes in the Gas Phase – Ion Mobility-Resolved Action-FRET. J. Am. Soc. Mass Spectrom. 2018;29:133–139. PubMed
Caleman C. Huldt G. Maia F. R. N. C. Ortiz C. Parak F. G. Hajdu J. van der Spoel D. Chapman H. N. Timneanu N. On the Feasibility of Nanocrystal Imaging Using Intense and Ultrashort X-ray Pulses. ACS Nano. 2011;5:139–146. PubMed
Papanastasiou D. Kounadis D. Lekkas A. Orfanopoulos I. Mpozatzidis A. Smyrnakis A. Panagiotopoulos E. Kosmopoulou M. Reinhardt-Szyba M. Fort K. Makarov A. Zubarev R. A. The Omnitrap Platform: A Versatile Segmented Linear Ion Trap for Multidimensional Multiple-Stage Tandem Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2022;33:1990–2007. PubMed PMC
Östlin C. Tîmneanu N. Jönsson H. O. Ekeberg T. Martin A. V. Caleman C. Reproducibility of single protein explosions induced by X-ray lasers. Phys. Chem. Chem. Phys. 2018;20:12381–12389. PubMed
De Santis E. Dawod I. André T. Cardoch S. Timneanu N. Caleman C. Ultrafast X-ray laser-induced explosion: How the depth influences the direction of the ion trajectory. Europhys. Lett. 2024;148:17001.
Snijder J. Schuller J. M. Wiegard A. Lössl P. Schmelling N. Axmann I. M. Plitzko J. M. Förster F. Heck A. J. R. Structures of the cyanobacterial circadian oscillator frozen in a fully assembled state. Science. 2017;355:1181–1184. PubMed
Sänger L. Williams H. M. Yu D. Vogel D. Kosinski J. Rosenthal M. Uetrecht C. RNA to Rule Them All: Critical Steps in Lassa Virus Ribonucleoparticle Assembly and Recruitment. J. Am. Chem. Soc. 2023;145:27958–27974. PubMed PMC
Zangl R. Soravia S. Saft M. Löffler J. G. Schulte J. Rosner C. J. Bredenbeck J. Essen L.-O. Morgner N. Time-Resolved Ion Mobility Mass Spectrometry to Solve Conformational Changes in a Cryptochrome. J. Am. Chem. Soc. 2024;146:14468–14478. PubMed
Schamoni-Kast K. Krichel B. Damjanović T. Kierspel T. Toker S. Uetrecht C. The kinetics of SARS-CoV-2 nsp7-11 polyprotein processing and impact on complexation with nsp16. bioRxiv. 2024 doi: 10.1101/2024.01.06.574466. DOI