A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
02 Dec 2023
Historique:
received: 23 02 2023
accepted: 10 11 2023
medline: 4 12 2023
pubmed: 3 12 2023
entrez: 2 12 2023
Statut: epublish

Résumé

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs. Compared to a standard single extruder, sample exchange time was halved and the workload of users was greatly reduced. In-built temperature control of samples facilitated optimal extrusion and supported sample stability. After commissioning the device with lysozyme crystals, we collected time-resolved data using crystals of a membrane-bound, light-driven sodium pump. Static data were also collected from the soluble protein tubulin that was soaked with a series of small molecule drugs. Using these data, we identify low occupancy (as little as 30%) ligands using a minimal amount of data from a serial crystallography experiment, a result that could be exploited for structure-based drug design.

Identifiants

pubmed: 38042952
doi: 10.1038/s41467-023-43523-5
pii: 10.1038/s41467-023-43523-5
pmc: PMC10693631
doi:

Substances chimiques

Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7956

Subventions

Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 310030_192566
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 31003A_179351
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 310030_207462
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TH2231/1-1

Informations de copyright

© 2023. The Author(s).

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Auteurs

Maximilian Wranik (M)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland. maximilian.wranik@psi.ch.

Michal W Kepa (MW)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland. michal.kepa@psi.ch.

Emma V Beale (EV)

Laboratory for Synchrotron Radiation and Femtochemistry, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Daniel James (D)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

Quentin Bertrand (Q)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

Tobias Weinert (T)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

Antonia Furrer (A)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

Hannah Glover (H)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

Dardan Gashi (D)

Laboratory for Synchrotron Radiation and Femtochemistry, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Melissa Carrillo (M)

Laboratory of Nanoscale Biology, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Yasushi Kondo (Y)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

Robin T Stipp (RT)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

Georgii Khusainov (G)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

Karol Nass (K)

Laboratory for Macromolecules and Bioimaging, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Dmitry Ozerov (D)

Scientific Computing, Theory and Data Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Claudio Cirelli (C)

Laboratory for Synchrotron Radiation and Femtochemistry, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Philip J M Johnson (PJM)

Laboratory for Nonlinear Optics, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Florian Dworkowski (F)

Laboratory for Macromolecules and Bioimaging, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

John H Beale (JH)

Laboratory for Macromolecules and Bioimaging, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Scott Stubbs (S)

Large Research Facilities Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Thierry Zamofing (T)

Large Research Facilities Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Marco Schneider (M)

Large Research Facilities Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Kristina Krauskopf (K)

Department of Pharmacy, Ludwig-Maximilians University of Munich, Butenandtstr. 7, Munich, 81377, Germany.

Li Gao (L)

Department of Pharmacy, Ludwig-Maximilians University of Munich, Butenandtstr. 7, Munich, 81377, Germany.

Oliver Thorn-Seshold (O)

Department of Pharmacy, Ludwig-Maximilians University of Munich, Butenandtstr. 7, Munich, 81377, Germany.

Christoph Bostedt (C)

Laboratory for Synchrotron Radiation and Femtochemistry, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.
LUXS Laboratory for Ultrafast X-ray Sciences, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland.

Camila Bacellar (C)

Laboratory for Synchrotron Radiation and Femtochemistry, Photon Science Division, Paul Scherrer Institut, Villigen-PSI, 5232, Villigen, Switzerland.

Michel O Steinmetz (MO)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.
Biozentrum, University of Basel, 4056, Basel, Switzerland.

Christopher Milne (C)

Femtosecond X-ray Experiments Instrument, European XFEL GmbH, Schenefeld, Germany.

Jörg Standfuss (J)

Laboratory of Biomolecular Research, Division of Biology and Chemistry, Paul Scherrer Institut, Villigen-PSI, Villigen, 5232, Switzerland.

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