Femtosecond X-ray protein nanocrystallography

Henry N. Chapman, Petra Fromme, Anton Barty, Thomas A. White, Richard A. Kirian, Andrew Aquila, Mark S. Hunter, Joachim Schulz, Daniel P. Deponte, Uwe Weierstall, R. Bruce Doak, Filipe R N C Maia, Andrew V. Martin, Ilme Schlichting, Lukas Lomb, Nicola Coppola, Robert L. Shoeman, Sascha W. Epp, Robert Hartmann, Daniel RollesArtem Rudenko, Lutz Foucar, Nils Kimmel, Georg Weidenspointner, Peter Holl, Mengning Liang, Miriam Barthelmess, Carl Caleman, Sébastien Boutet, Michael J. Bogan, Jacek Krzywinski, Christoph Bostedt, Sǎa Bajt, Lars Gumprecht, Benedikt Rudek, Benjamin Erk, Carlo Schmidt, André Hömke, Christian Reich, Daniel Pietschner, Lothar Ströder, Günter Hauser, Hubert Gorke, Joachim Ullrich, Sven Herrmann, Gerhard Schaller, Florian Schopper, Heike Soltau, Kai Uwe Kühnel, Marc Messerschmidt, John D. Bozek, Stefan P. Hau-Riege, Matthias Frank, Christina Y. Hampton, Raymond G. Sierra, Dmitri Starodub, Garth J. Williams, Janos Hajdu, Nicusor Timneanu, M. Marvin Seibert, Jakob Andreasson, Andrea Rocker, Olof Jönsson, Martin Svenda, Stephan Stern, Karol Nass, Robert Andritschke, Claus Dieter Schröter, Faton Krasniqi, Mario Bott, Kevin E. Schmidt, Xiaoyu Wang, Ingo Grotjohann, James M. Holton, Thomas R M Barends, Richard Neutze, Stefano Marchesini, Raimund Fromme, Sebastian Schorb, Daniela Rupp, Marcus Adolph, Tais Gorkhover, Inger Andersson, Helmut Hirsemann, Guillaume Potdevin, Heinz Graafsma, Björn Nilsson, John C H Spence

Research output: Contribution to journalArticle

1199 Citations (Scopus)

Abstract

X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction snapshotsg are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (4200nm to 21/4m in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.

Original languageEnglish
Pages (from-to)73-78
Number of pages6
JournalNature
Volume470
Issue number7332
DOIs
Publication statusPublished - Feb 3 2011

Fingerprint

Nanoparticles
Photosystem I Protein Complex
X-Rays
Radiation
Membrane Proteins
Crystallography
Proteins
X Ray Crystallography
X-Ray Diffraction
Lasers
Electrons
Light
Datasets

ASJC Scopus subject areas

  • General

Cite this

Chapman, H. N., Fromme, P., Barty, A., White, T. A., Kirian, R. A., Aquila, A., ... Spence, J. C. H. (2011). Femtosecond X-ray protein nanocrystallography. Nature, 470(7332), 73-78. https://doi.org/10.1038/nature09750

Femtosecond X-ray protein nanocrystallography. / Chapman, Henry N.; Fromme, Petra; Barty, Anton; White, Thomas A.; Kirian, Richard A.; Aquila, Andrew; Hunter, Mark S.; Schulz, Joachim; Deponte, Daniel P.; Weierstall, Uwe; Doak, R. Bruce; Maia, Filipe R N C; Martin, Andrew V.; Schlichting, Ilme; Lomb, Lukas; Coppola, Nicola; Shoeman, Robert L.; Epp, Sascha W.; Hartmann, Robert; Rolles, Daniel; Rudenko, Artem; Foucar, Lutz; Kimmel, Nils; Weidenspointner, Georg; Holl, Peter; Liang, Mengning; Barthelmess, Miriam; Caleman, Carl; Boutet, Sébastien; Bogan, Michael J.; Krzywinski, Jacek; Bostedt, Christoph; Bajt, Sǎa; Gumprecht, Lars; Rudek, Benedikt; Erk, Benjamin; Schmidt, Carlo; Hömke, André; Reich, Christian; Pietschner, Daniel; Ströder, Lothar; Hauser, Günter; Gorke, Hubert; Ullrich, Joachim; Herrmann, Sven; Schaller, Gerhard; Schopper, Florian; Soltau, Heike; Kühnel, Kai Uwe; Messerschmidt, Marc; Bozek, John D.; Hau-Riege, Stefan P.; Frank, Matthias; Hampton, Christina Y.; Sierra, Raymond G.; Starodub, Dmitri; Williams, Garth J.; Hajdu, Janos; Timneanu, Nicusor; Seibert, M. Marvin; Andreasson, Jakob; Rocker, Andrea; Jönsson, Olof; Svenda, Martin; Stern, Stephan; Nass, Karol; Andritschke, Robert; Schröter, Claus Dieter; Krasniqi, Faton; Bott, Mario; Schmidt, Kevin E.; Wang, Xiaoyu; Grotjohann, Ingo; Holton, James M.; Barends, Thomas R M; Neutze, Richard; Marchesini, Stefano; Fromme, Raimund; Schorb, Sebastian; Rupp, Daniela; Adolph, Marcus; Gorkhover, Tais; Andersson, Inger; Hirsemann, Helmut; Potdevin, Guillaume; Graafsma, Heinz; Nilsson, Björn; Spence, John C H.

In: Nature, Vol. 470, No. 7332, 03.02.2011, p. 73-78.

Research output: Contribution to journalArticle

Chapman, HN, Fromme, P, Barty, A, White, TA, Kirian, RA, Aquila, A, Hunter, MS, Schulz, J, Deponte, DP, Weierstall, U, Doak, RB, Maia, FRNC, Martin, AV, Schlichting, I, Lomb, L, Coppola, N, Shoeman, RL, Epp, SW, Hartmann, R, Rolles, D, Rudenko, A, Foucar, L, Kimmel, N, Weidenspointner, G, Holl, P, Liang, M, Barthelmess, M, Caleman, C, Boutet, S, Bogan, MJ, Krzywinski, J, Bostedt, C, Bajt, S, Gumprecht, L, Rudek, B, Erk, B, Schmidt, C, Hömke, A, Reich, C, Pietschner, D, Ströder, L, Hauser, G, Gorke, H, Ullrich, J, Herrmann, S, Schaller, G, Schopper, F, Soltau, H, Kühnel, KU, Messerschmidt, M, Bozek, JD, Hau-Riege, SP, Frank, M, Hampton, CY, Sierra, RG, Starodub, D, Williams, GJ, Hajdu, J, Timneanu, N, Seibert, MM, Andreasson, J, Rocker, A, Jönsson, O, Svenda, M, Stern, S, Nass, K, Andritschke, R, Schröter, CD, Krasniqi, F, Bott, M, Schmidt, KE, Wang, X, Grotjohann, I, Holton, JM, Barends, TRM, Neutze, R, Marchesini, S, Fromme, R, Schorb, S, Rupp, D, Adolph, M, Gorkhover, T, Andersson, I, Hirsemann, H, Potdevin, G, Graafsma, H, Nilsson, B & Spence, JCH 2011, 'Femtosecond X-ray protein nanocrystallography', Nature, vol. 470, no. 7332, pp. 73-78. https://doi.org/10.1038/nature09750
Chapman HN, Fromme P, Barty A, White TA, Kirian RA, Aquila A et al. Femtosecond X-ray protein nanocrystallography. Nature. 2011 Feb 3;470(7332):73-78. https://doi.org/10.1038/nature09750
Chapman, Henry N. ; Fromme, Petra ; Barty, Anton ; White, Thomas A. ; Kirian, Richard A. ; Aquila, Andrew ; Hunter, Mark S. ; Schulz, Joachim ; Deponte, Daniel P. ; Weierstall, Uwe ; Doak, R. Bruce ; Maia, Filipe R N C ; Martin, Andrew V. ; Schlichting, Ilme ; Lomb, Lukas ; Coppola, Nicola ; Shoeman, Robert L. ; Epp, Sascha W. ; Hartmann, Robert ; Rolles, Daniel ; Rudenko, Artem ; Foucar, Lutz ; Kimmel, Nils ; Weidenspointner, Georg ; Holl, Peter ; Liang, Mengning ; Barthelmess, Miriam ; Caleman, Carl ; Boutet, Sébastien ; Bogan, Michael J. ; Krzywinski, Jacek ; Bostedt, Christoph ; Bajt, Sǎa ; Gumprecht, Lars ; Rudek, Benedikt ; Erk, Benjamin ; Schmidt, Carlo ; Hömke, André ; Reich, Christian ; Pietschner, Daniel ; Ströder, Lothar ; Hauser, Günter ; Gorke, Hubert ; Ullrich, Joachim ; Herrmann, Sven ; Schaller, Gerhard ; Schopper, Florian ; Soltau, Heike ; Kühnel, Kai Uwe ; Messerschmidt, Marc ; Bozek, John D. ; Hau-Riege, Stefan P. ; Frank, Matthias ; Hampton, Christina Y. ; Sierra, Raymond G. ; Starodub, Dmitri ; Williams, Garth J. ; Hajdu, Janos ; Timneanu, Nicusor ; Seibert, M. Marvin ; Andreasson, Jakob ; Rocker, Andrea ; Jönsson, Olof ; Svenda, Martin ; Stern, Stephan ; Nass, Karol ; Andritschke, Robert ; Schröter, Claus Dieter ; Krasniqi, Faton ; Bott, Mario ; Schmidt, Kevin E. ; Wang, Xiaoyu ; Grotjohann, Ingo ; Holton, James M. ; Barends, Thomas R M ; Neutze, Richard ; Marchesini, Stefano ; Fromme, Raimund ; Schorb, Sebastian ; Rupp, Daniela ; Adolph, Marcus ; Gorkhover, Tais ; Andersson, Inger ; Hirsemann, Helmut ; Potdevin, Guillaume ; Graafsma, Heinz ; Nilsson, Björn ; Spence, John C H. / Femtosecond X-ray protein nanocrystallography. In: Nature. 2011 ; Vol. 470, No. 7332. pp. 73-78.
@article{7d585714c70c49899ee9c51832c726bd,
title = "Femtosecond X-ray protein nanocrystallography",
abstract = "X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction snapshotsg are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (4200nm to 21/4m in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.",
author = "Chapman, {Henry N.} and Petra Fromme and Anton Barty and White, {Thomas A.} and Kirian, {Richard A.} and Andrew Aquila and Hunter, {Mark S.} and Joachim Schulz and Deponte, {Daniel P.} and Uwe Weierstall and Doak, {R. Bruce} and Maia, {Filipe R N C} and Martin, {Andrew V.} and Ilme Schlichting and Lukas Lomb and Nicola Coppola and Shoeman, {Robert L.} and Epp, {Sascha W.} and Robert Hartmann and Daniel Rolles and Artem Rudenko and Lutz Foucar and Nils Kimmel and Georg Weidenspointner and Peter Holl and Mengning Liang and Miriam Barthelmess and Carl Caleman and S{\'e}bastien Boutet and Bogan, {Michael J.} and Jacek Krzywinski and Christoph Bostedt and Sǎa Bajt and Lars Gumprecht and Benedikt Rudek and Benjamin Erk and Carlo Schmidt and Andr{\'e} H{\"o}mke and Christian Reich and Daniel Pietschner and Lothar Str{\"o}der and G{\"u}nter Hauser and Hubert Gorke and Joachim Ullrich and Sven Herrmann and Gerhard Schaller and Florian Schopper and Heike Soltau and K{\"u}hnel, {Kai Uwe} and Marc Messerschmidt and Bozek, {John D.} and Hau-Riege, {Stefan P.} and Matthias Frank and Hampton, {Christina Y.} and Sierra, {Raymond G.} and Dmitri Starodub and Williams, {Garth J.} and Janos Hajdu and Nicusor Timneanu and Seibert, {M. Marvin} and Jakob Andreasson and Andrea Rocker and Olof J{\"o}nsson and Martin Svenda and Stephan Stern and Karol Nass and Robert Andritschke and Schr{\"o}ter, {Claus Dieter} and Faton Krasniqi and Mario Bott and Schmidt, {Kevin E.} and Xiaoyu Wang and Ingo Grotjohann and Holton, {James M.} and Barends, {Thomas R M} and Richard Neutze and Stefano Marchesini and Raimund Fromme and Sebastian Schorb and Daniela Rupp and Marcus Adolph and Tais Gorkhover and Inger Andersson and Helmut Hirsemann and Guillaume Potdevin and Heinz Graafsma and Bj{\"o}rn Nilsson and Spence, {John C H}",
year = "2011",
month = "2",
day = "3",
doi = "10.1038/nature09750",
language = "English",
volume = "470",
pages = "73--78",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7332",

}

TY - JOUR

T1 - Femtosecond X-ray protein nanocrystallography

AU - Chapman, Henry N.

AU - Fromme, Petra

AU - Barty, Anton

AU - White, Thomas A.

AU - Kirian, Richard A.

AU - Aquila, Andrew

AU - Hunter, Mark S.

AU - Schulz, Joachim

AU - Deponte, Daniel P.

AU - Weierstall, Uwe

AU - Doak, R. Bruce

AU - Maia, Filipe R N C

AU - Martin, Andrew V.

AU - Schlichting, Ilme

AU - Lomb, Lukas

AU - Coppola, Nicola

AU - Shoeman, Robert L.

AU - Epp, Sascha W.

AU - Hartmann, Robert

AU - Rolles, Daniel

AU - Rudenko, Artem

AU - Foucar, Lutz

AU - Kimmel, Nils

AU - Weidenspointner, Georg

AU - Holl, Peter

AU - Liang, Mengning

AU - Barthelmess, Miriam

AU - Caleman, Carl

AU - Boutet, Sébastien

AU - Bogan, Michael J.

AU - Krzywinski, Jacek

AU - Bostedt, Christoph

AU - Bajt, Sǎa

AU - Gumprecht, Lars

AU - Rudek, Benedikt

AU - Erk, Benjamin

AU - Schmidt, Carlo

AU - Hömke, André

AU - Reich, Christian

AU - Pietschner, Daniel

AU - Ströder, Lothar

AU - Hauser, Günter

AU - Gorke, Hubert

AU - Ullrich, Joachim

AU - Herrmann, Sven

AU - Schaller, Gerhard

AU - Schopper, Florian

AU - Soltau, Heike

AU - Kühnel, Kai Uwe

AU - Messerschmidt, Marc

AU - Bozek, John D.

AU - Hau-Riege, Stefan P.

AU - Frank, Matthias

AU - Hampton, Christina Y.

AU - Sierra, Raymond G.

AU - Starodub, Dmitri

AU - Williams, Garth J.

AU - Hajdu, Janos

AU - Timneanu, Nicusor

AU - Seibert, M. Marvin

AU - Andreasson, Jakob

AU - Rocker, Andrea

AU - Jönsson, Olof

AU - Svenda, Martin

AU - Stern, Stephan

AU - Nass, Karol

AU - Andritschke, Robert

AU - Schröter, Claus Dieter

AU - Krasniqi, Faton

AU - Bott, Mario

AU - Schmidt, Kevin E.

AU - Wang, Xiaoyu

AU - Grotjohann, Ingo

AU - Holton, James M.

AU - Barends, Thomas R M

AU - Neutze, Richard

AU - Marchesini, Stefano

AU - Fromme, Raimund

AU - Schorb, Sebastian

AU - Rupp, Daniela

AU - Adolph, Marcus

AU - Gorkhover, Tais

AU - Andersson, Inger

AU - Hirsemann, Helmut

AU - Potdevin, Guillaume

AU - Graafsma, Heinz

AU - Nilsson, Björn

AU - Spence, John C H

PY - 2011/2/3

Y1 - 2011/2/3

N2 - X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction snapshotsg are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (4200nm to 21/4m in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.

AB - X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction snapshotsg are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (4200nm to 21/4m in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.

UR - http://www.scopus.com/inward/record.url?scp=79551658540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551658540&partnerID=8YFLogxK

U2 - 10.1038/nature09750

DO - 10.1038/nature09750

M3 - Article

C2 - 21293373

AN - SCOPUS:79551658540

VL - 470

SP - 73

EP - 78

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7332

ER -