Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron
Abstract Serial macromolecular crystallography has become a powerful method to reveal room temperature structures of biological macromolecules and perform time-resolved studies. ID29, a flagship beamline of the ESRF 4th generation synchrotron, is the first synchrotron beamline in the world capable o...
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Nature Portfolio
2025-01-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-024-01404-y |
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| author | Julien Orlans Samuel L. Rose Gavin Ferguson Marcus Oscarsson Alejandro Homs Puron Antonia Beteva Samuel Debionne Pascal Theveneau Nicolas Coquelle Jerome Kieffer Paolo Busca Jeremy Sinoir Victor Armijo Marcos Lopez Marrero Franck Felisaz Gergely Papp Herve Gonzalez Hugo Caserotto Fabien Dobias Jonathan Gigmes Guillaume Lebon Shibom Basu Daniele de Sanctis |
| author_facet | Julien Orlans Samuel L. Rose Gavin Ferguson Marcus Oscarsson Alejandro Homs Puron Antonia Beteva Samuel Debionne Pascal Theveneau Nicolas Coquelle Jerome Kieffer Paolo Busca Jeremy Sinoir Victor Armijo Marcos Lopez Marrero Franck Felisaz Gergely Papp Herve Gonzalez Hugo Caserotto Fabien Dobias Jonathan Gigmes Guillaume Lebon Shibom Basu Daniele de Sanctis |
| author_sort | Julien Orlans |
| collection | DOAJ |
| description | Abstract Serial macromolecular crystallography has become a powerful method to reveal room temperature structures of biological macromolecules and perform time-resolved studies. ID29, a flagship beamline of the ESRF 4th generation synchrotron, is the first synchrotron beamline in the world capable of delivering high brilliance microsecond X-ray pulses at high repetition rate for the structure determination of biological macromolecules at room temperature. The cardinal combination of microsecond exposure times, innovative beam characteristics and adaptable sample environment provides high quality complete data, even from an exceptionally small amount of crystalline material, enabling what we collectively term serial microsecond crystallography (SµX). After validating the use of different sample delivery methods with various model systems, we applied SµX to an integral membrane receptor, where only a few thousands diffraction images were sufficient to obtain a fully interpretable electron density map for the antagonist istradefylline-bound A2A receptor conformation, providing access to the antagonist binding mode. SµX, as demonstrated at ID29, will quickly find its broad applicability at upcoming 4th generation synchrotron sources worldwide and opens a new frontier in time-resolved SµX. |
| format | Article |
| id | doaj-art-cf4b013e2b7d406f80b03928c881008e |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-cf4b013e2b7d406f80b03928c881008e2025-01-12T12:11:18ZengNature PortfolioCommunications Chemistry2399-36692025-01-018111210.1038/s42004-024-01404-yAdvancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotronJulien Orlans0Samuel L. Rose1Gavin Ferguson2Marcus Oscarsson3Alejandro Homs Puron4Antonia Beteva5Samuel Debionne6Pascal Theveneau7Nicolas Coquelle8Jerome Kieffer9Paolo Busca10Jeremy Sinoir11Victor Armijo12Marcos Lopez Marrero13Franck Felisaz14Gergely Papp15Herve Gonzalez16Hugo Caserotto17Fabien Dobias18Jonathan Gigmes19Guillaume Lebon20Shibom Basu21Daniele de Sanctis22ESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERMESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsEuropean Molecular Biology Laboratory, 71 Avenue des MartyrsEuropean Molecular Biology Laboratory, 71 Avenue des MartyrsEuropean Molecular Biology Laboratory, 71 Avenue des MartyrsEuropean Molecular Biology Laboratory, 71 Avenue des MartyrsEuropean Molecular Biology Laboratory, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERMEuropean Molecular Biology Laboratory, 71 Avenue des MartyrsESRF - The European Synchrotron, 71 Avenue des MartyrsAbstract Serial macromolecular crystallography has become a powerful method to reveal room temperature structures of biological macromolecules and perform time-resolved studies. ID29, a flagship beamline of the ESRF 4th generation synchrotron, is the first synchrotron beamline in the world capable of delivering high brilliance microsecond X-ray pulses at high repetition rate for the structure determination of biological macromolecules at room temperature. The cardinal combination of microsecond exposure times, innovative beam characteristics and adaptable sample environment provides high quality complete data, even from an exceptionally small amount of crystalline material, enabling what we collectively term serial microsecond crystallography (SµX). After validating the use of different sample delivery methods with various model systems, we applied SµX to an integral membrane receptor, where only a few thousands diffraction images were sufficient to obtain a fully interpretable electron density map for the antagonist istradefylline-bound A2A receptor conformation, providing access to the antagonist binding mode. SµX, as demonstrated at ID29, will quickly find its broad applicability at upcoming 4th generation synchrotron sources worldwide and opens a new frontier in time-resolved SµX.https://doi.org/10.1038/s42004-024-01404-y |
| spellingShingle | Julien Orlans Samuel L. Rose Gavin Ferguson Marcus Oscarsson Alejandro Homs Puron Antonia Beteva Samuel Debionne Pascal Theveneau Nicolas Coquelle Jerome Kieffer Paolo Busca Jeremy Sinoir Victor Armijo Marcos Lopez Marrero Franck Felisaz Gergely Papp Herve Gonzalez Hugo Caserotto Fabien Dobias Jonathan Gigmes Guillaume Lebon Shibom Basu Daniele de Sanctis Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron Communications Chemistry |
| title | Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron |
| title_full | Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron |
| title_fullStr | Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron |
| title_full_unstemmed | Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron |
| title_short | Advancing macromolecular structure determination with microsecond X-ray pulses at a 4th generation synchrotron |
| title_sort | advancing macromolecular structure determination with microsecond x ray pulses at a 4th generation synchrotron |
| url | https://doi.org/10.1038/s42004-024-01404-y |
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