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Title: Single-particle structure determination by X-ray free-electron lasers: Possibilities and challenges

Abstract

Single-particle structure recovery without crystals or radiation damage is a revolutionary possibility offered by X-ray free-electron lasers, but it involves formidable experimental and data-analytical challenges. Many of these difficulties were encountered during the development of cryogenic electron microscopy of biological systems. Electron microscopy of biological entities has now reached a spatial resolution of about 0.3 nm, with a rapidly emerging capability to map discrete and continuous conformational changes and the energy landscapes of biomolecular machines. Nonetheless, single-particle imaging by X-ray freeelectron lasers remains important for a range of applications, including the study of large “electron-opaque” objects and time-resolved examination of key biological processes at physiological temperatures. After summarizing the state of the art in the study of structure and conformations by cryogenic electron microscopy, we identify the primary opportunities and challenges facing X-ray-based single-particle approaches, and possible means for circumventing them.

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. Univ. of Wisconsin, Milwaukee, WI (United States)
Publication Date:
Research Org.:
Univ. of Wisconsin, Milwaukee, WI (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Science Foundation (NSF)
OSTI Identifier:
1598194
Alternate Identifier(s):
OSTI ID: 1421053
Grant/Contract Number:  
FG02-09ER16114; SC0002164
Resource Type:
Accepted Manuscript
Journal Name:
Structural Dynamics
Additional Journal Information:
Journal Volume: 2; Journal Issue: 4; Journal ID: ISSN 2329-7778
Publisher:
American Crystallographic Association/AIP
Country of Publication:
United States
Language:
English
Subject:
71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSICS

Citation Formats

Hosseinizadeh, A., Dashti, A., Schwander, P., Fung, R., and Ourmazd, A. Single-particle structure determination by X-ray free-electron lasers: Possibilities and challenges. United States: N. p., 2015. Web. doi:10.1063/1.4919740.
Hosseinizadeh, A., Dashti, A., Schwander, P., Fung, R., & Ourmazd, A. Single-particle structure determination by X-ray free-electron lasers: Possibilities and challenges. United States. https://doi.org/10.1063/1.4919740
Hosseinizadeh, A., Dashti, A., Schwander, P., Fung, R., and Ourmazd, A. Thu . "Single-particle structure determination by X-ray free-electron lasers: Possibilities and challenges". United States. https://doi.org/10.1063/1.4919740. https://www.osti.gov/servlets/purl/1598194.
@article{osti_1598194,
title = {Single-particle structure determination by X-ray free-electron lasers: Possibilities and challenges},
author = {Hosseinizadeh, A. and Dashti, A. and Schwander, P. and Fung, R. and Ourmazd, A.},
abstractNote = {Single-particle structure recovery without crystals or radiation damage is a revolutionary possibility offered by X-ray free-electron lasers, but it involves formidable experimental and data-analytical challenges. Many of these difficulties were encountered during the development of cryogenic electron microscopy of biological systems. Electron microscopy of biological entities has now reached a spatial resolution of about 0.3 nm, with a rapidly emerging capability to map discrete and continuous conformational changes and the energy landscapes of biomolecular machines. Nonetheless, single-particle imaging by X-ray freeelectron lasers remains important for a range of applications, including the study of large “electron-opaque” objects and time-resolved examination of key biological processes at physiological temperatures. After summarizing the state of the art in the study of structure and conformations by cryogenic electron microscopy, we identify the primary opportunities and challenges facing X-ray-based single-particle approaches, and possible means for circumventing them.},
doi = {10.1063/1.4919740},
journal = {Structural Dynamics},
number = 4,
volume = 2,
place = {United States},
year = {Thu Apr 30 00:00:00 EDT 2015},
month = {Thu Apr 30 00:00:00 EDT 2015}
}

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Works referenced in this record:

Single-shot three-dimensional structure determination of nanocrystals with femtosecond X-ray free-electron laser pulses
journal, June 2014

  • Xu, Rui; Jiang, Huaidong; Song, Changyong
  • Nature Communications, Vol. 5, Issue 1
  • DOI: 10.1038/ncomms5061

Bayesian algorithms for recovering structure from single-particle diffraction snapshots of unknown orientation: a comparison
journal, July 2011

  • Moths, Brian; Ourmazd, Abbas
  • Acta Crystallographica Section A Foundations of Crystallography, Vol. 67, Issue 5
  • DOI: 10.1107/S0108767311019611

A Bayesian View on Cryo-EM Structure Determination
journal, January 2012


Crystallography without crystals. I. The common-line method for assembling a three-dimensional diffraction volume from single-particle scattering
journal, February 2008

  • Shneerson, V. L.; Ourmazd, A.; Saldin, D. K.
  • Acta Crystallographica Section A Foundations of Crystallography, Vol. 64, Issue 2
  • DOI: 10.1107/S0108767307067621

Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser
journal, March 2015


Conformations of macromolecules and their complexes from heterogeneous datasets
journal, July 2014

  • Schwander, P.; Fung, R.; Ourmazd, A.
  • Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 369, Issue 1647
  • DOI: 10.1098/rstb.2013.0567

High-resolution structure of viruses from random diffraction snapshots
journal, July 2014

  • Hosseinizadeh, A.; Schwander, P.; Dashti, A.
  • Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 369, Issue 1647
  • DOI: 10.1098/rstb.2013.0326

Solving structure with sparse, randomly-oriented x-ray data
journal, January 2012

  • Philipp, Hugh T.; Ayyer, Kartik; Tate, Mark W.
  • Optics Express, Vol. 20, Issue 12
  • DOI: 10.1364/OE.20.013129

The symmetries of image formation by scattering I Theoretical framework
journal, January 2012

  • Giannakis, Dimitrios; Schwander, Peter; Ourmazd, Abbas
  • Optics Express, Vol. 20, Issue 12
  • DOI: 10.1364/OE.20.012799

Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization
journal, December 2006

  • Scheres, Sjors H. W.; Gao, Haixiao; Valle, Mikel
  • Nature Methods, Vol. 4, Issue 1
  • DOI: 10.1038/nmeth992

Microholography of Living Organisms
journal, October 1982


How Should We Think About the Ribosome?
journal, June 2012


Signal, noise, and resolution in correlated fluctuations from snapshot small-angle x-ray scattering
journal, July 2011


Structure of the human LAT1–4F2hc heteromeric amino acid transporter complex
journal, March 2019


Flat-field correction technique for digital detectors
conference, July 1998

  • Seibert, James A.; Boone, John M.; Lindfors, Karen K.
  • Medical Imaging '98, SPIE Proceedings
  • DOI: 10.1117/12.317034

Reconstruction algorithm for single-particle diffraction imaging experiments
journal, August 2009


The symmetries of image formation by scattering II Applications
journal, January 2012

  • Schwander, Peter; Giannakis, Dimitrios; Yoon, Chun Hong
  • Optics Express, Vol. 20, Issue 12
  • DOI: 10.1364/OE.20.012827

Structure from fleeting illumination of faint spinning objects in flight
journal, November 2008

  • Fung, Russell; Shneerson, Valentin; Saldin, Dilano K.
  • Nature Physics, Vol. 5, Issue 1
  • DOI: 10.1038/nphys1129

Atomic structure of a single large biomolecule from diffraction patterns of random orientations
journal, July 2012


Potential for biomolecular imaging with femtosecond X-ray pulses
journal, August 2000

  • Neutze, Richard; Wouts, Remco; van der Spoel, David
  • Nature, Vol. 406, Issue 6797
  • DOI: 10.1038/35021099

The linac coherent light source single particle imaging road map
journal, July 2015

  • Aquila, A.; Barty, A.; Bostedt, C.
  • Structural Dynamics, Vol. 2, Issue 4
  • DOI: 10.1063/1.4918726

Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization
book, April 2018


Structure of the Yeast Mitochondrial Large Ribosomal Subunit
journal, March 2014


Structure of isolated biomolecules obtained from ultrashort x-ray pulses: exploiting the symmetry of random orientations
journal, March 2009


Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy
journal, July 2010

  • Fischer, Niels; Konevega, Andrey L.; Wintermeyer, Wolfgang
  • Nature, Vol. 466, Issue 7304
  • DOI: 10.1038/nature09206

Trajectories of the ribosome as a Brownian nanomachine
journal, November 2014

  • Dashti, Ali; Schwander, Peter; Langlois, Robert
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 49
  • DOI: 10.1073/pnas.1419276111

Structure of the Yeast Mitochondrial Large Ribosomal Subunit
journal, August 2014


A reconstruction algorithm for single-particle diffraction imaging experiments
journal, August 2009

  • Loh, Duane Ne-Te; Elser, Veit
  • Acta Crystallographica Section A Foundations of Crystallography, Vol. 65, Issue a1
  • DOI: 10.1107/s0108767309098584

A Bayesian view on cryo-EM structure determination
conference, May 2012

  • Scheres, Sjors H. W.
  • 2012 IEEE 9th International Symposium on Biomedical Imaging (ISBI 2012), 2012 9th IEEE International Symposium on Biomedical Imaging (ISBI)
  • DOI: 10.1109/isbi.2012.6235807

Conformations of Macromolecules and their Complexes from Heterogeneous Datasets
preprint, January 2014


High-resolution structure of viruses from random diffraction snapshots
preprint, January 2014


Atomic structure of a single large biomolecule from diffraction patterns of random orientations
journal, July 2012


Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy
journal, July 2010

  • Fischer, Niels; Konevega, Andrey L.; Wintermeyer, Wolfgang
  • Nature, Vol. 466, Issue 7304
  • DOI: 10.1038/nature09206

Single-shot three-dimensional structure determination of nanocrystals with femtosecond X-ray free-electron laser pulses
journal, June 2014

  • Xu, Rui; Jiang, Huaidong; Song, Changyong
  • Nature Communications, Vol. 5, Issue 1
  • DOI: 10.1038/ncomms5061

Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization
journal, December 2006

  • Scheres, Sjors H. W.; Gao, Haixiao; Valle, Mikel
  • Nature Methods, Vol. 4, Issue 1
  • DOI: 10.1038/nmeth992

Cryo-EM, XFELs and the structure conundrum in structural biology
journal, September 2019


The linac coherent light source single particle imaging road map
journal, July 2015

  • Aquila, A.; Barty, A.; Bostedt, C.
  • Structural Dynamics, Vol. 2, Issue 4
  • DOI: 10.1063/1.4918726

High-resolution structure of viruses from random diffraction snapshots
journal, July 2014

  • Hosseinizadeh, A.; Schwander, P.; Dashti, A.
  • Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 369, Issue 1647
  • DOI: 10.1098/rstb.2013.0326

A Bayesian view on cryo-EM structure determination
conference, May 2012

  • Scheres, Sjors H. W.
  • 2012 IEEE 9th International Symposium on Biomedical Imaging (ISBI 2012), 2012 9th IEEE International Symposium on Biomedical Imaging (ISBI)
  • DOI: 10.1109/isbi.2012.6235807

Flat-field correction technique for digital detectors
conference, July 1998

  • Seibert, James A.; Boone, John M.; Lindfors, Karen K.
  • Medical Imaging '98, SPIE Proceedings
  • DOI: 10.1117/12.317034

Works referencing / citing this record:

Short-wavelength free-electron laser sources and science: a review
text, January 2017

  • Seddon, E. A.; Clarke, J. A.; Dunning, D. J.
  • Deutsches Elektronen-Synchrotron, DESY, Hamburg
  • DOI: 10.3204/pubdb-2018-00596

Coherent diffraction of single Rice Dwarf virus particles using hard X-rays at the Linac Coherent Light Source
text, January 2016

  • Munke, Anna; Andreasson, Jakob; Aquila, Andrew
  • Deutsches Elektronen-Synchrotron, DESY, Hamburg
  • DOI: 10.3204/pubdb-2016-02771

Conformational landscape of a virus by single-particle X-ray scattering
journal, August 2017

  • Hosseinizadeh, Ahmad; Mashayekhi, Ghoncheh; Copperman, Jeremy
  • Nature Methods, Vol. 14, Issue 9
  • DOI: 10.1038/nmeth.4395

Coherent diffraction of single Rice Dwarf virus particles using hard X-rays at the Linac Coherent Light Source
journal, August 2016

  • Munke, Anna; Andreasson, Jakob; Aquila, Andrew
  • Scientific Data, Vol. 3, Issue 1
  • DOI: 10.1038/sdata.2016.64

Coherent soft X-ray diffraction imaging of coliphage PR772 at the Linac coherent light source
journal, June 2017

  • Reddy, Hemanth K. N.; Yoon, Chun Hong; Aquila, Andrew
  • Scientific Data, Vol. 4, Issue 1
  • DOI: 10.1038/sdata.2017.79

Evaluation of the performance of classification algorithms for XFEL single-particle imaging data
journal, February 2019


Evaluation of the performance of classification algorithms for XFEL single-particle imaging data
text, January 2019


Evaluation of the performance of classification algorithms for XFEL single-particle imaging data
text, January 2019


Short-wavelength free-electron laser sources and science: a review
journal, October 2017

  • Seddon, E. A.; Clarke, J. A.; Dunning, D. J.
  • Reports on Progress in Physics, Vol. 80, Issue 11
  • DOI: 10.1088/1361-6633/aa7cca

Single-particle imaging by x-ray free-electron lasers—How many snapshots are needed?
journal, March 2020

  • Poudyal, I.; Schmidt, M.; Schwander, P.
  • Structural Dynamics, Vol. 7, Issue 2
  • DOI: 10.1063/1.5144516

A Survey of the Use of Iterative Reconstruction Algorithms in Electron Microscopy
journal, January 2017

  • Sorzano, C. O. S.; Vargas, J.; Otón, J.
  • BioMed Research International, Vol. 2017
  • DOI: 10.1155/2017/6482567