Publications
List of publications which include the data collected on the facility instruments.
- Grba, D. N., Wright, J. J., Yin, Z., Fisher, W. & Hirst, J. Molecular mechanism of the ischemia-induced regulatory switch in mammalian complex I. Science 384, 1247–1253 (2024).
https://doi.org/10.1126/science.ado2075 - Meynier V, Hardwick SW, Catala M, Roske JJ, Oerum S, Chirgadze DY, Barraud P, Yue WW, Luisi BF, Tisné C. Structural basis for human mitochondrial tRNA maturation. Nature Communications (2024) Jun 1;15(1):4683.
https://doi.org/10.1038/s41467-024-49132-0. - Kasaragod VB, Malinauskas T, Wahid AA, Lengyel J, Knoflach F, Hardwick SW, Jones CF, Chen WN, Lucas X, El Omari K, Chirgadze DY, Aricescu AR, Cecere G, Hernandez MC, Miller PS. The molecular basis of drug selectivity for α5 subunit-containing GABAA receptors. Nature Structural & Molecular Biology (2023) Dec;30(12):1936-1946.
https://doi.org/10.1038/s41594-023-01133-1. - Kefala Stavridi A, Gontier A, Morin V, Frit P, Ropars V, Barboule N, Racca C, Jonchhe S, Morten MJ, Andreani J, Rak A, Legrand P, Bourand-Plantefol A, Hardwick SW, Chirgadze DY, Davey P, De Oliveira TM, Rothenberg E, Britton S, Calsou P, Blundell TL, Varela PF, Chaplin AK, Charbonnier JB. Structural and functional basis of inositol hexaphosphate stimulation of NHEJ through stabilization of Ku-XLF interaction. Nucleic Acids Res. (2023) Nov 27;51(21):11732-11747.
https://doi.org/10.1093/nar/gkad863 - Hardwick SW, Stavridi AK, Chirgadze DY, De Oliveira TM, Charbonnier JB, Ropars V, Meek K, Blundell TL, Chaplin AK. Cryo-EM structure of a DNA-PK trimer: higher order oligomerisation in NHEJ. Structure (2023) May 31:S0969-2126(23)00167-3.
https://doi.org/10.1016/j.str.2023.05.013. - Agip, A.-N. A., Chung, I., Sanchez-Martinez, A., Whitworth, A. J. & Hirst, J. Cryo-EM structures of mitochondrial respiratory complex I from Drosophila melanogaster. eLife 12, (2023).
https://doi.org/10.7554/eLife.84424. - Seif-El-Dahan M, Kefala-Stavridi A, Frit P, Hardwick SW, Chirgadze DY, Maia De Oliviera T, Britton S, Barboule N, Bossaert M, Pandurangan AP, Meek K, Blundell TL, Ropars V, Calsou P, Charbonnier JB, Chaplin AK. PAXX binding to the NHEJ machinery explains functional redundancy with XLF. Science Advances (2023) Jun 2;9(22):eadg2834.
https://doi.org/10.1126/sciadv.adg2834 - Appleby R, Bollschweiler D, Chirgadze DY, Joudeh L, Pellegrini L. A metal ion-dependent mechanism of RAD51 nucleoprotein filament disassembly. iScience. (2023) Apr 25;26(5):106689.
https://doi.org/10.1016/j.isci.2023.106689 - Islam MS, Hardwick SW, Quell L, Durica-Mitic S, Chirgadze DY, Görke B, Luisi BF. Structure of a bacterial ribonucleoprotein complex central to the control of cell envelope biogenesis.
EMBO J. (2023) Jan 16;42(2):e112574.
https://doi.org/10.15252/embj.2022112574. - Wilson LFL, Dendooven T, Hardwick SW, Echevarría-Poza A, Tryfona T, Krogh KBRM, Chirgadze DY, Luisi BF, Logan DT, Mani K, Dupree P. The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis. Nature Communications (2022) Jun 8;13(1):3314.
https://doi.org/10.1038/s41467-022-31048-2. - Chung I, Wright JJ, Bridges HR, Ivanov BS, Biner O, Pereira CS, Arantes GM, Hirst J. Cryo-EM structures define ubiquinone-10 binding to mitochondrial complex I and conformational transitions accompanying Q-site occupancy. Nature Communications (2022) May 19;13(1):2758.
https://doi.org/10.1038/s41467-022-30506-1. - De Bei O, Marchetti M, Ronda L, Gianquinto E, Lazzarato L, Chirgadze DY, Hardwick SW, Cooper LR, Spyrakis F, Luisi BF, Campanini B, Bettati S. Cryo-EM structures of staphylococcal IsdB bound to human hemoglobin reveal the process of heme extraction. Proc Natl Acad Sci U S A. (2022) Apr 5;119(14):e2116708119.
https://doi.org/10.1073/pnas.2116708119. - Sente A, Desai R, Naydenova K, Malinauskas T, Jounaidi Y, Miehling J, Zhou X, Masiulis S, Hardwick SW, Chirgadze DY, Miller KW, Aricescu AR. Differential assembly diversifies GABAA receptor structures and signalling. Nature (2022) Apr;604(7904):190-194.
https://doi.org/10.1038/s41586-022-04517-3 - Kasaragod VB, Mortensen M, Hardwick SW, Wahid AA, Dorovykh V, Chirgadze DY, Smart TG, Miller PS. Mechanisms of inhibition and activation of extrasynaptic αβ GABAAreceptors. Nature (2022) Feb;602(7897):529-533.
https://doi.org/10.1038/s41586-022-04402-z - Liang, S., Thomas, S.E., Chaplin, A.K. Hardwick, S.W., Chirgadze, D.Y. and Blundell, T.L. Structural insights into inhibitor regulation of the DNA repair protein DNA-PKcs. Nature 601, 643–648 (2022).
https://doi.org/10.1038/s41586-021-04274-9 - Rebelo-Guiomar P, Pellegrino S, Dent KC, Sas-Chen A, Miller-Fleming L, Garone C, Van Haute L, Rogan JF, Dinan A, Firth AE, Andrews B, Whitworth AJ, Schwartz S, Warren AJ, Minczuk M. A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit. Nature Communications (2022) Feb 17;13(1):929.
https://doi.org/10.1038/s41467-022-28503-5. - Kilkenny, M.L., Veale, C.E., Guppy, A., Hardwick, S.W, Chirgadze, D.Y., Rzechorzek, N.J., Maman, J.D. and Pellegrini, L. Structural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with DNA polymerase α-primase. Protein Science 31(2):333-344 (2022).
https://doi.org/10.1002/pro.4220 - Dendooven. T., Paris, G., Shkumatov, A.V., Islam, M.S., Burt, A., Kubańska, M.A., Yang, T.Y., Hardwick, S.W. and Luisi, B.F. Multi-scale ensemble properties of the Escherichia coli RNA degradosome. Molecular Microbiology Jan;117(1):102-120 (2022).
https://doi.org/10.1111/mmi.14800 - Yan, Y., Harding, H.P. & Ron, D. Higher-order phosphatase–substrate contacts terminate the integrated stress response. Nature Structural and Molecular Biology 28, 835–846 (2021).
https://doi.org/10.1038/s41594-021-00666-7 - Yin, Z., Burger, N., Kula-Alwar, D., Aksentijević, D., Bridges, H. R., Prag, H. A., Grba, D. N., Viscomi, C., James, A.M., Mottahedin, A., Krieg, T., Murphy, M.P. and Hirst, J. Structural basis for a complex I mutation that blocks pathological ROS production. Nature Communications volume 12, Article number: 707 (2021).
https://doi.org/10.13039/501100009187 - Hameedi, M. A. et al. A conserved arginine residue is critical for stabilizing the N2 FeS cluster in mitochondrial complex I. Journal of Biological Chemistry 296, 100474 (2021).
- Harris, A., Wagner, M., Du, D., Raschka, S., Nentwig, L.-M., Gohlke, H., Smits, S.H.J., Luisi, B.F. and Schmitt, L. Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5. Nature Communications 12, 5254 (2021).
https://doi.org/10.1038/s41467-021-25574-8 - Munir, A., Wilson, M.T., Hardwick, S.W., Chirgadze, D.Y., Worrall, J.A.R., Blundell, T.L. and Chaplin, A.K. Using cryo-EM to understand antimycobacterial resistance in the catalase-peroxidase (KatG) from Mycobacterium tuberculosis. Structure. Aug 5;29(8):899-912.e4 (2021).
https://doi.org/10.1016/j.str.2020.12.008 - Dendooven, T., Sinha, D., Roeselová, A., Cameron, T.A., De Lay, N.R., Luisi, B.F. and Bandyra, K.J. A cooperative PNPase-Hfq-RNA carrier complex facilitates bacterial riboregulation. Molecular Cell. 81(14):2901-2913.e5 (2021).
https://doi.org/10.1016/j.molcel.2021.05.032 - Spikes, T.E., Montgomery, M.G. and Walker, J.E. Interface mobility between monomers in dimeric bovine ATP synthase participates in the ultrastructure of inner mitochondrial membranes. PNAS 118 (8) e2021012118 (2021).
https://doi.org/10.1073/pnas.2021012118 - Chaplin, A.K., Hardwick, S.W., Liang, S. Kefala Stavridi, A., Hnizda, A., Cooper, L.R., De Oliveira, T.M., Chirgadze, D.Y. and Blundell, T.L. Dimers of DNA-PK create a stage for DNA double-strand break repair. Nature Structural and Molecular Biology 28, 13–19 (2021).
https://doi.org/10.1038/s41594-020-00517-x - Chaplin, A.K., Hardwick, S.W., Kefala Stavridi, A., Buehl, C.J., Goff, N.J., Ropas, Liang, S., De Oliveira, T.M., Chirgadze, D.Y., Meek, K., Charbonnier, J.-B. and Blundell, T.L. Cryo-EM of NHEJ supercomplexes provides insights into DNA repair. Molecular Cell, Volume 81(16):3400-3409 (2021).
https://doi.org/10.1016/j.molcel.2021.07.005 - Grba, D.N. and Hirst J. Mitochondrial complex I structure reveals ordered water molecules for catalysis and proton translocation. Nature Structural & Molecular Biology volume 27, pages 892–900 (2020).
https://doi.org/10.1038/s41594-020-0473-x - Du., D, Neuberger, A., Wu Orr, M., Newman, C.E. Hsu, P.-C., Samsudin, F., Szewczak-Harris, A., Ramos, L.M., Debela, M., Khalid, S., Storz, G. and Luisi, B.F. Interactions of a Bacterial RND Transporter with a Transmembrane Small Protein in a Lipid Environment. Structure, Volume 28, Issue 6, Pages 625-634 (2020).
https://doi.org/10.1016/j.str.2020.03.013. - Oerum S, Dendooven T, Catala M, Gilet L, Dégut C, Trinquier A, Bourguet M, Barraud P, Cianferani S, Luisi BF, Condon C, Tisné C. Structures of B. subtilis Maturation RNases Captured on 50S Ribosome with Pre-rRNAs. Molecular Cell, Volume 80 (2):227-236 (2020).
https://doi.org/10.1016/j.molcel.2020.09.008. - Spikes, T.E., Montgomery, M.G., and Walker, J.E. Structure of the dimeric ATP synthase from bovine mitochondria. PNAS 117 (38) 23519-23526 (2020).
https://doi.org/10.1073/pnas.2013998117 - Nakane, T., Kotecha, A., Sente, A., McMullan, G., Masiulis, S., Brown, P.M.G.E., Grigoras, I.T., Malinauskaite, L., Malinauskas, T., Miehling, J., Yu, L., Karia, D., Pechnikova, E.V., de Jong, E., Keizer, J., Bischoff, M., McCormack, J., Tiemeijer, P., Hardwick, S.W., Chirgadze, D.Y., Murshudov, G., Aricescu, A.R. and Scheres, S,H.W. Single-particle cryo-EM at atomic resolution. Nature587:152–156 (2020).
https://doi.org/10.1038/s41586-020-2829-0 - Hill, C.H., Napthine, S,, Pekarek, L., Kibe, A., Firth, A.E., Graham, S.C., Caliskan, N. and Brierley, I. Structural studies of Cardiovirus 2A protein reveal the molecular basis for RNA recognition and translational control. BioRxiv 08.11.245035 (2020).
https://doi.org/10.1101/2020.08.11.245035 - Biner, O., Fedor, J., Yin, Z. and Hirst, J. Bottom-Up Construction of a Minimal System for Cellular Respiration and Energy Regeneration. ACS Synthetic Biology. 9 (6): 1450-1459 (2020).
https://doi.org/10.1021/acssynbio.0c00110. - Rzechorzek, N.J., Hardwick, S.W., Jatikusumo, V.A., Chirgadze, D.Y. and Pellegrini, L. Cryo-EM structures of human CMG–ATPγS–DNA and CMG–AND-1 complexes. Nucleic Acids Research 48 (12):6980-6995 (2020). PMID: 32453425
https://doi.org/10.1093/nar/gkaa429 - Kovtun, O., Dickson, V.K., Kelly, B.T., Owen, D.J. and Briggs, J.A.G. Architecture of the AP2/clathrin coat on the membranes of clathrin-coated vesicles. Science Advances. 6 (30):eaba 8381 (2020). PMID: 32743075
https://doi.org/10.1126/sciadv.aba8381 - Moncrieffe, M.C., Bollschweiler, D., Li, B., Penczek, P.A., Hopkins, L., Bryant, C.E., Klenerman, D. and Gay, N.J. MyD88 death-domain oligomerization determines myddosome architecture: implications for Toll-like receptor signaling. Structure 28 (3):281-289 (2020). PMID: 31995744.
https://doi.org/10.1016/j.str.2020.01.003 - Charenton, C., Wilkinson, M.E. and Nagai, K. Mechanism of 5ʹ splice site transfer for human spliceosome activation. Science 364 (6438):362-367 (2019). PMID 30975767.
https://doi.org/10.1126/science.aax3289 - Wu, Q., Liang, S., Ochi, T., Chirgadze, D.Y., Huiskonen, J.T. and Blundell, T.L. Understanding the structure and role of DNA-PK in NHEJ: How X-ray diffraction and cryo-EM contribute in complementary ways. Progress in Biophysics and Molecular Biology 147:26-32 (2019). PMID: 31014919
https://doi.org/10.1016/j.pbiomolbio.2019.03.007 - Kargas, V., Castro-Hartmann, P., Escudero-Urquijo, N., Dent, K., Hilcenko, C., Sailer, C., Zisser, G., Marques-Carvalho, M.J., Pellegrino, S., Wawiórka, L., Freund, S.M., Wagstaff, J.L., Andreeva, A., Faille, A., Chen, E., Stengel, F., Bergler, H. and Warren A.J. Mechanism of completion of peptidyltransferase centre assembly in eukaryotes. Elife 8 (2019). PMID: 31115337.
https://doi.org/10.7554/eLife.44904 - Yu, Q., Qu, K. and Modis, Y. Cryo-EM Structures of MDA5-dsRNA Filaments at Different Stages of ATP Hydrolysis. Molecular Cell, 72 (6):999-1012 (2018). PMID: 30449722.
https://doi.org/10.1016/j.molcel.2018.10.012