Chap4Resp SIGNED
Catching in action a novel bacterial chaperone for respiratory complexes
Total Cost €
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Project "Chap4Resp" data sheet
The following table provides information about the project.
| Coordinator |
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Organization address contact info |
| Coordinator Country | France [FR] |
| Project website | http://www.ibs.fr/research/research-groups/methods-and-electron-microscopy-group/gutsche-team/ |
| Total cost | 1˙999˙956 € |
| EC max contribution | 1˙999˙956 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-CoG |
| Funding Scheme | ERC-COG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-10-01 to 2021-09-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS | FR (PARIS) | coordinator | 1˙999˙956.00 |
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Project objective
Cellular respiration provides energy to power essential processes of life. Respiratory complexes are macromolecular batteries coupling electron flow through a wire of metal clusters and cofactors with proton transfer across the inner membrane of mitochondria and bacteria. Waste products of these cellular factories are reactive oxygen species causing ageing and diseases. Assembly and maturation mechanisms of respiratory complexes remain enigmatic because of their membrane location, multisubunit composition and cofactor insertion. E. coli Complex I, one of the largest membrane proteins, composed of 14 conserved subunits with 9 Fe/S clusters and a flavin, is a minimal model for its 45-subunit human homologue. When proton pumping by respiratory complexes is affected, bacteria become resistant to antibiotics requiring proton gradient for uptake. Based on the latest genetic data, we realize that the huge E. coli macromolecular cage, the structure of which we recently solved by cryo-electron microscopy (cryoEM), in conjunction with a novel protein cofactor, is a specific chaperone for Fe/S cluster biogenesis and assembly of respiratory complexes. This integrated multidisciplinary project combines cryoEM and other structural, biophysical and spectroscopic techniques, to uncover the functional mechanism of this emerging chaperone. The structural plasticity of the chaperone fuelled by ATP hydrolysis, and its interaction with Fe/S cluster biogenesis systems and the main respiratory complexes as a function of stresses, will be scrutinized to gain quasiatomic insights into the way the chaperone operates on its substrates. A novel technology for synergetic in situ investigation of protein complexes in the bacterial cytoplasm by optical imaging, state-of-the-art cryogenic correlative light and electron microscopy, and subtomogram analysis, will be developed and used to obtain snapshots of the chaperone-substrate interactions in the cellular context.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2020 |
Alister Burt, C. Keith Cassidy, Peter Ames, Maria Bacia-Verloop, Megghane Baulard, Karine Huard, Zaida Luthey-Schulten, Ambroise Desfosses, Phillip J. Stansfeld, William Margolin, John S. Parkinson, Irina Gutsche Complete structure of the chemosensory array core signalling unit in an E. coli minicell strain published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-020-14350-9 |
Nature Communications 11/1 | 2020-04-15 |
| 2019 |
Rosalba Lepore, Andriy Kryshtafovych, Markus Alahuhta, Harshul A. Veraszto, Yannick J. Bomble, Joshua C. Bufton, Alex N. Bullock, Cody Caba, Hongnan Cao, Owen R. Davies, Ambroise Desfosses, Matthew Dunne, Krzysztof Fidelis, Celia W. Goulding, Manickam Gurusaran, Irina Gutsche, Christopher J. Harding, Marcus D. Hartmann, Christopher S. Hayes, Andrzej Joachimiak, Petr G. Leiman, Peter Loppnau, Andre Target highlights in CASP13: Experimental target structures through the eyes of their authors published pages: 1037-1057, ISSN: 0887-3585, DOI: 10.1002/prot.25805 |
Proteins: Structure, Function, and Bioinformatics 87/12 | 2020-04-15 |
| 2019 |
Kandiah E, Carriel D, Garcia PS, Felix J, Banzhaf M, Kritikos G, Bacia-Verloop M, Brochier-Armanet C, Elsen S, Gutsche I. Structure, Function, and Evolution of the Pseudomonas aeruginosa Lysine Decarboxylase LdcA published pages: 1842-1854, ISSN: 0969-2126, DOI: 10.1016/j.str.2019.10.003 |
Structure Dec 3;27(12) | 2020-04-15 |
| 2020 |
Matthew Jessop, Benoit Arragain, Roger Miras, Angélique Fraudeau, Karine Huard, Maria Bacia-Verloop, Patrice Catty, Jan Felix, Hélène Malet, Irina Gutsche Structural insights into ATP hydrolysis by the MoxR ATPase RavA and the LdcI-RavA cage-like complex published pages: , ISSN: 2399-3642, DOI: 10.1038/s42003-020-0772-0 |
Communications Biology 3/1 | 2020-04-15 |
| 2019 |
Ambroise Desfosses, Hariprasad Venugopal, Tapan Joshi, Jan Felix, Matthew Jessop, Hyengseop Jeong, Jaekyung Hyun, J. Bernard Heymann, Mark R. H. Hurst, Irina Gutsche, Alok K. Mitra Atomic structures of an entire contractile injection system in both the extended and contracted states published pages: 1885-1894, ISSN: 2058-5276, DOI: 10.1038/s41564-019-0530-6 |
Nature Microbiology 4/11 | 2020-04-15 |
| 2019 |
Firas Khatib, Ambroise Desfosses, Brian Koepnick, Jeff Flatten, Zoran Popović, David Baker, Seth Cooper, Irina Gutsche, Scott Horowitz Building de novo cryo-electron microscopy structures collaboratively with citizen scientists published pages: e3000472, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.3000472 |
PLOS Biology 17/11 | 2020-04-15 |
| 2019 |
Federica Laddomada, Mayara M. Miyachiro, Matthew Jessop, Delphine Patin, Viviana Job, Dominique Mengin-Lecreulx, Aline Le Roy, Christine Ebel, Cécile Breyton, Irina Gutsche, Andréa Dessen The MurG glycosyltransferase provides an oligomeric scaffold for the cytoplasmic steps of peptidoglycan biosynthesis in the human pathogen Bordetella pertussis published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-019-40966-z |
Scientific Reports 9/1 | 2020-04-15 |
| 2019 |
Koen H. G. Verschueren, Clement Blanchet, Jan Felix, Ann Dansercoer, Dirk De Vos, Yehudi Bloch, Jozef Van Beeumen, Dmitri Svergun, Irina Gutsche, Savvas N. Savvides, Kenneth Verstraete Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle published pages: 571-575, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1095-5 |
Nature 568/7753 | 2020-04-15 |
| 2016 |
Eaazhisai Kandiah, Diego Carriel, Julien Perard, Hélène Malet, Maria Bacia, Kaiyin Liu, Sze W. S. Chan, Walid A. Houry, Sandrine Ollagnier de Choudens, Sylvie Elsen, Irina Gutsche Structural insights into the Escherichia coli lysine decarboxylases andmolecular determinants of interaction with the AAA+ ATPase RavA published pages: , ISSN: 2045-2322, DOI: 10.1038/srep24601 |
Scientific Reports 6/1 | 2019-10-14 |
| 2018 |
Diego Carriel, Pierre Simon Garcia, Florence Castelli, Patricia Lamourette, François Fenaille, Céline Brochier-Armanet, Sylvie Elsen, Irina Gutsche A novel subfamily of bacterial AAT-fold basic amino acid decarboxylases and functional characterization of its first representative: Pseudomonas aeruginosa LdcA published pages: , ISSN: 1759-6653, DOI: 10.1093/gbe/evy228 |
Genome Biology and Evolution | 2019-10-14 |
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