--- _id: '8318' abstract: - lang: eng text: Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I. acknowledgement: This work was funded by the Medical Research Council, UK and IST Austria. We thank the European Synchrotron Radiation Facility and the Diamond Light Source for provision of synchrotron radiation facilities. We are grateful to the staff of beamlines ID29, ID23-2 (ESRF, Grenoble, France) and I03 (Diamond Light Source, Didcot, UK) for assistance. Data processing was performed at the IST high-performance computing cluster. article_number: '4135' article_processing_charge: No article_type: original author: - first_name: Javier full_name: Gutierrez-Fernandez, Javier id: 3D9511BA-F248-11E8-B48F-1D18A9856A87 last_name: Gutierrez-Fernandez - first_name: Karol full_name: Kaszuba, Karol id: 3FDF9472-F248-11E8-B48F-1D18A9856A87 last_name: Kaszuba - first_name: Gurdeep S. full_name: Minhas, Gurdeep S. last_name: Minhas - first_name: Rozbeh full_name: Baradaran, Rozbeh last_name: Baradaran - first_name: Margherita full_name: Tambalo, Margherita id: 4187dfe4-ec23-11ea-ae46-f08ab378313a last_name: Tambalo - first_name: David T. full_name: Gallagher, David T. last_name: Gallagher - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 citation: ama: Gutierrez-Fernandez J, Kaszuba K, Minhas GS, et al. Key role of quinone in the mechanism of respiratory complex I. Nature Communications. 2020;11(1). doi:10.1038/s41467-020-17957-0 apa: Gutierrez-Fernandez, J., Kaszuba, K., Minhas, G. S., Baradaran, R., Tambalo, M., Gallagher, D. T., & Sazanov, L. A. (2020). Key role of quinone in the mechanism of respiratory complex I. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-17957-0 chicago: Gutierrez-Fernandez, Javier, Karol Kaszuba, Gurdeep S. Minhas, Rozbeh Baradaran, Margherita Tambalo, David T. Gallagher, and Leonid A Sazanov. “Key Role of Quinone in the Mechanism of Respiratory Complex I.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17957-0. ieee: J. Gutierrez-Fernandez et al., “Key role of quinone in the mechanism of respiratory complex I,” Nature Communications, vol. 11, no. 1. Springer Nature, 2020. ista: Gutierrez-Fernandez J, Kaszuba K, Minhas GS, Baradaran R, Tambalo M, Gallagher DT, Sazanov LA. 2020. Key role of quinone in the mechanism of respiratory complex I. Nature Communications. 11(1), 4135. mla: Gutierrez-Fernandez, Javier, et al. “Key Role of Quinone in the Mechanism of Respiratory Complex I.” Nature Communications, vol. 11, no. 1, 4135, Springer Nature, 2020, doi:10.1038/s41467-020-17957-0. short: J. Gutierrez-Fernandez, K. Kaszuba, G.S. Minhas, R. Baradaran, M. Tambalo, D.T. Gallagher, L.A. Sazanov, Nature Communications 11 (2020). date_created: 2020-08-30T22:01:10Z date_published: 2020-08-18T00:00:00Z date_updated: 2023-08-22T09:03:00Z day: '18' ddc: - '570' department: - _id: LeSa doi: 10.1038/s41467-020-17957-0 external_id: isi: - '000607072900001' pmid: - '32811817' file: - access_level: open_access checksum: 52b96f41d7d0db9728064c08da00d030 content_type: application/pdf creator: cziletti date_created: 2020-08-31T13:40:00Z date_updated: 2020-08-31T13:40:00Z file_id: '8326' file_name: 2020_NatComm_Gutierrez-Fernandez.pdf file_size: 7527373 relation: main_file success: 1 file_date_updated: 2020-08-31T13:40:00Z has_accepted_license: '1' intvolume: ' 11' isi: 1 issue: '1' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '08' oa: 1 oa_version: Published Version pmid: 1 publication: Nature Communications publication_identifier: eissn: - '20411723' publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - description: News on IST Homepage relation: press_release url: https://ist.ac.at/en/news/mystery-of-giant-proton-pump-solved/ scopus_import: '1' status: public title: Key role of quinone in the mechanism of respiratory complex I tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2020' ... --- _id: '1186' abstract: - lang: eng text: The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus. acknowledgement: We gratefully acknowledge Karsta Barnekow and Kristine Sievert-Giermann, for technical assistance and Lothar Petruschka for in silico analysis (all Dept. of Genetics, University of Greifswald). We are further grateful to the staff from SLS synchrotron beamline for help in data collection. This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG GRK 1870 (to SH) and the Spanish Ministry of Economy and Competitiveness (BFU2014-59389-P to JAH, CTQ2014-52633-P to MB and SAF2012-39760-C02-02 to FG) and S2010/BMD-2457 (Community of Madrid to JAH and FG). article_number: '38094' author: - first_name: Javier full_name: Gutierrez-Fernandez, Javier id: 3D9511BA-F248-11E8-B48F-1D18A9856A87 last_name: Gutierrez-Fernandez - first_name: Malek full_name: Saleh, Malek last_name: Saleh - first_name: Martín full_name: Alcorlo, Martín last_name: Alcorlo - first_name: Alejandro full_name: Gómez Mejóa, Alejandro last_name: Gómez Mejóa - first_name: David full_name: Pantoja Uceda, David last_name: Pantoja Uceda - first_name: Miguel full_name: Treviño, Miguel last_name: Treviño - first_name: Franziska full_name: Vob, Franziska last_name: Vob - first_name: Mohammed full_name: Abdullah, Mohammed last_name: Abdullah - first_name: Sergio full_name: Galán Bartual, Sergio last_name: Galán Bartual - first_name: Jolien full_name: Seinen, Jolien last_name: Seinen - first_name: Pedro full_name: Sánchez Murcia, Pedro last_name: Sánchez Murcia - first_name: Federico full_name: Gago, Federico last_name: Gago - first_name: Marta full_name: Bruix, Marta last_name: Bruix - first_name: Sven full_name: Hammerschmidt, Sven last_name: Hammerschmidt - first_name: Juan full_name: Hermoso, Juan last_name: Hermoso citation: ama: Gutierrez-Fernandez J, Saleh M, Alcorlo M, et al. Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. 2016;6. doi:10.1038/srep38094 apa: Gutierrez-Fernandez, J., Saleh, M., Alcorlo, M., Gómez Mejóa, A., Pantoja Uceda, D., Treviño, M., … Hermoso, J. (2016). Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/srep38094 chicago: Gutierrez-Fernandez, Javier, Malek Saleh, Martín Alcorlo, Alejandro Gómez Mejóa, David Pantoja Uceda, Miguel Treviño, Franziska Vob, et al. “Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L CbpL Contributing to Pneumococcal Pathogenesis.” Scientific Reports. Nature Publishing Group, 2016. https://doi.org/10.1038/srep38094. ieee: J. Gutierrez-Fernandez et al., “Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis,” Scientific Reports, vol. 6. Nature Publishing Group, 2016. ista: Gutierrez-Fernandez J, Saleh M, Alcorlo M, Gómez Mejóa A, Pantoja Uceda D, Treviño M, Vob F, Abdullah M, Galán Bartual S, Seinen J, Sánchez Murcia P, Gago F, Bruix M, Hammerschmidt S, Hermoso J. 2016. Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis. Scientific Reports. 6, 38094. mla: Gutierrez-Fernandez, Javier, et al. “Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L CbpL Contributing to Pneumococcal Pathogenesis.” Scientific Reports, vol. 6, 38094, Nature Publishing Group, 2016, doi:10.1038/srep38094. short: J. Gutierrez-Fernandez, M. Saleh, M. Alcorlo, A. Gómez Mejóa, D. Pantoja Uceda, M. Treviño, F. Vob, M. Abdullah, S. Galán Bartual, J. Seinen, P. Sánchez Murcia, F. Gago, M. Bruix, S. Hammerschmidt, J. Hermoso, Scientific Reports 6 (2016). date_created: 2018-12-11T11:50:36Z date_published: 2016-12-05T00:00:00Z date_updated: 2021-01-12T06:48:56Z day: '05' ddc: - '576' - '610' department: - _id: LeSa doi: 10.1038/srep38094 file: - access_level: open_access checksum: e007d78b483bc59bf5ab98e9d42a6ec1 content_type: application/pdf creator: system date_created: 2018-12-12T10:10:18Z date_updated: 2020-07-14T12:44:37Z file_id: '4804' file_name: IST-2017-735-v1+1_srep38094.pdf file_size: 2716045 relation: main_file file_date_updated: 2020-07-14T12:44:37Z has_accepted_license: '1' intvolume: ' 6' language: - iso: eng month: '12' oa: 1 oa_version: Published Version publication: Scientific Reports publication_status: published publisher: Nature Publishing Group publist_id: '6167' pubrep_id: '735' quality_controlled: '1' scopus_import: 1 status: public title: Modular architecture and unique teichoic acid recognition features of choline-binding protein L CbpL contributing to pneumococcal pathogenesis tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 6 year: '2016' ...