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Research Facilities at the Department of Biochemistry

 

 

Publications

List of publications which include the data collected on the facility instruments.

  1. Hooda Y, Sente A, Judy RM, Smalinskaitė L, Peak-Chew SY, Naydenova K, Malinauskas T, Hardwick SW, Chirgadze DY, Aricescu AR, Hegde RS. Mechanism of NACHO-mediated assembly of pentameric ligand-gated ion channels. bioRxiv [Preprint]. Nov 15:2024.10.28.620708 (2024).
    https://doi.org/10.1101/2024.10.28.620708
  2. Lewis WH, Paris G, Beedessee G, Kořený L, Flores V, Dendooven T, Gallet B, Yee DP, Lam S, Decelle J, Luisi BF, Waller RF. Plastid translocon recycling in dinoflagellates demonstrates the portability of complex plastids between hosts. Curr Biol. Dec 2;34(23):5494-5506.e3. (2024)
    https://doi.org/10.1016/j.cub.2024.10.034
  3. Yin Z, Kilkenny ML, Ker DS, Pellegrini L. CryoEM insights into RNA primer synthesis by the human primosome. FEBS J. 2024 Apr;291(8):1813-1829 (2024).
    https://doi.org/10.1111/febs.17082
  4. Hanthi YW, Ramirez-Otero MA, Appleby R, De Antoni A, Joudeh L, Sannino V, Waked S, Ardizzoia A, Barra V, Fachinetti D, Pellegrini L, Costanzo V. RAD51 protects abasic sites to prevent replication fork breakage. Mol Cell. 2024 Aug 22;84(16):3026-3043.e11 (2024).
    https://doi.org/10.1016/j.molcel.2024.07.004
  5. 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
  6. Ivanov BS, Bridges HR, Jarman OD, Hirst J. Structure of the turnover-ready state of an ancestral respiratory complex I. Nat Commun. Oct 29;15(1):9340. (2024)
    https://doi.org/10.1038/s41467-024-53679-3
  7. 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
  8. 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
  9. Faille A, Dent KC, Pellegrino S, Jaako P, Warren AJ. The chemical landscape of the human ribosome at 1.67 Å resolution. bioRxiv [Preprint]. 2023 Feb 28:2023.02.28.530191 (2023).
    https://doi.org/10.1101/2023.02.28.530191.
  10. Pellegrino S, Dent KC, Spikes T, Warren AJ. Cryo-EM reconstruction of the human 40S ribosomal subunit at 2.15 Å resolution. Nucleic Acids Res.2023 May 8;51(8):4043-4054 (2023).
    https://doi.org/10.1093/nar/gkad194
  11. Appleby R, Joudeh L, Cobbett K, Pellegrini L. Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2. Nat Commun. 2023 Nov 2;14(1):7003 (2023).
    https://doi.org/10.1038/s41467-023-42830-1
  12. 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
  13. 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.
  14. 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 
  15. Buehl CJ, Goff NJ, Mikhova M, Hardwick SW, Blundell TL, Modesti M, Schmidt JC, Chaplin A, Meek K. Unravelling the complexities of DNA-PK activation by structure-based mutagenesis. Res Sq [Preprint]. 2023 Dec 13:rs.3.rs-3627471. (2023)
    https://doi.org/10.21203/rs.3.rs-3627471/v1
  16. 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
  17. 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
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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
  23. 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
  24. 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
  25. 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.
  26. 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
  27. 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
  28. Yan, Y., Harding, H.P. & Ron, D. Higher-order phosphatase–substrate contacts terminate the integrated stress response. Nature Structural and Molecular Biology 28835–846 (2021).
    https://doi.org/10.1038/s41594-021-00666-7
  29. 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
  30. 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).
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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.
  39. 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.
  40. 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
  41. 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
  42. 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
  43. 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.
  44. 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
  45. 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
  46. 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
  47. 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
  48. 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 
  49. 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
  50. 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