--- _id: '1980' abstract: - lang: eng text: Non-proton pumping type II NADH dehydrogenase (NDH-2) plays a central role in the respiratory metabolism of bacteria, and in the mitochondria of fungi, plants and protists. The lack of NDH-2 in mammalian mitochondria and its essentiality in important bacterial pathogens suggests these enzymes may represent a potential new drug target to combat microbial pathogens. Here, we report the first crystal structure of a bacterial NDH-2 enzyme at 2.5Å resolution from Caldalkalibacillus thermarum. The NDH-2 structure reveals a homodimeric organization that has a unique dimer interface. NDH-2 is localized to the cytoplasmic membrane by two separated C-terminal membrane-anchoring regions that are essential for membrane localization and FAD binding, but not NDH-2 dimerization. Comparison of bacterial NDH-2 with the yeast NADH dehydrogenase (Ndi1) structure revealed non-overlapping binding sites for quinone and NADH in the bacterial enzyme. The bacterial NDH-2 structure establishes a framework for the structure-based design of small-molecule inhibitors. acknowledgement: Funded by Health Research Council of New Zealand Royal Society of New Zealand University of Otago New Zealand Synchrotron Group author: - first_name: Adam full_name: 'Heikal, Adam ' last_name: Heikal - first_name: Yoshio full_name: Nakatani, Yoshio last_name: Nakatani - first_name: Elyse full_name: Dunn, Elyse A last_name: Dunn - first_name: Marion full_name: Weimar, Marion R last_name: Weimar - first_name: Catherine full_name: Day, Catherine last_name: Day - first_name: Edward full_name: Baker, Edward N last_name: Baker - first_name: Shaun full_name: Lott, Shaun J last_name: Lott - first_name: Leonid A full_name: Leonid Sazanov id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 - first_name: Gregory full_name: Cook, Gregory last_name: Cook citation: ama: 'Heikal A, Nakatani Y, Dunn E, et al. Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation. Molecular Microbiology. 2014;91(5):950-964. doi:10.1111/mmi.12507' apa: 'Heikal, A., Nakatani, Y., Dunn, E., Weimar, M., Day, C., Baker, E., … Cook, G. (2014). Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation. Molecular Microbiology. Wiley-Blackwell. https://doi.org/10.1111/mmi.12507' chicago: 'Heikal, Adam, Yoshio Nakatani, Elyse Dunn, Marion Weimar, Catherine Day, Edward Baker, Shaun Lott, Leonid A Sazanov, and Gregory Cook. “Structure of the Bacterial Type II NADH Dehydrogenase: A Monotopic Membrane Protein with an Essential Role in Energy Generation.” Molecular Microbiology. Wiley-Blackwell, 2014. https://doi.org/10.1111/mmi.12507.' ieee: 'A. Heikal et al., “Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation,” Molecular Microbiology, vol. 91, no. 5. Wiley-Blackwell, pp. 950–964, 2014.' ista: 'Heikal A, Nakatani Y, Dunn E, Weimar M, Day C, Baker E, Lott S, Sazanov LA, Cook G. 2014. Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation. Molecular Microbiology. 91(5), 950–964.' mla: 'Heikal, Adam, et al. “Structure of the Bacterial Type II NADH Dehydrogenase: A Monotopic Membrane Protein with an Essential Role in Energy Generation.” Molecular Microbiology, vol. 91, no. 5, Wiley-Blackwell, 2014, pp. 950–64, doi:10.1111/mmi.12507.' short: A. Heikal, Y. Nakatani, E. Dunn, M. Weimar, C. Day, E. Baker, S. Lott, L.A. Sazanov, G. Cook, Molecular Microbiology 91 (2014) 950–964. date_created: 2018-12-11T11:55:01Z date_published: 2014-03-01T00:00:00Z date_updated: 2021-01-12T06:54:29Z day: '01' doi: 10.1111/mmi.12507 extern: 1 intvolume: ' 91' issue: '5' month: '03' page: 950 - 964 publication: Molecular Microbiology publication_status: published publisher: Wiley-Blackwell publist_id: '5103' quality_controlled: 0 status: public title: 'Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation' type: journal_article volume: 91 year: '2014' ... --- _id: '1979' abstract: - lang: eng text: NADH-ubiquinone oxidoreductase (complex I) is the first and largest enzyme in the respiratory chain of mitochondria and many bacteria. It couples the transfer of two electrons between NADH and ubiquinone to the translocation of four protons across the membrane. Complex I is an L-shaped assembly formed by the hydrophilic (peripheral) arm, containing all the redox centres performing electron transfer and the membrane arm, containing proton-translocating machinery. Mitochondrial complex I consists of 44 subunits of about 1 MDa in total, whilst the prokaryotic enzyme is simpler and generally consists of 14 conserved “core” subunits. Recently we have determined the first atomic structure of the entire complex I, using the enzyme from Thermus thermophilus (536 kDa, 16 subunits, 9 Fe-S clusters, 64 TM helices). Structure suggests a unique coupling mechanism, with redox energy of electron transfer driving proton translocation via long-range (up to ~200 Å) conformational changes. It resembles a steam engine, with coupling elements (akin to coupling rods) linking parts of this molecular machine. author: - first_name: Leonid A full_name: Leonid Sazanov id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 citation: ama: Sazanov LA. The mechanism of coupling between electron transfer and proton translocation in respiratory complex I. Journal of Bioenergetics and Biomembranes. 2014;46(4):247-253. doi:10.1007/s10863-014-9554-z apa: Sazanov, L. A. (2014). The mechanism of coupling between electron transfer and proton translocation in respiratory complex I. Journal of Bioenergetics and Biomembranes. Springer. https://doi.org/10.1007/s10863-014-9554-z chicago: Sazanov, Leonid A. “The Mechanism of Coupling between Electron Transfer and Proton Translocation in Respiratory Complex I.” Journal of Bioenergetics and Biomembranes. Springer, 2014. https://doi.org/10.1007/s10863-014-9554-z. ieee: L. A. Sazanov, “The mechanism of coupling between electron transfer and proton translocation in respiratory complex I,” Journal of Bioenergetics and Biomembranes, vol. 46, no. 4. Springer, pp. 247–253, 2014. ista: Sazanov LA. 2014. The mechanism of coupling between electron transfer and proton translocation in respiratory complex I. Journal of Bioenergetics and Biomembranes. 46(4), 247–253. mla: Sazanov, Leonid A. “The Mechanism of Coupling between Electron Transfer and Proton Translocation in Respiratory Complex I.” Journal of Bioenergetics and Biomembranes, vol. 46, no. 4, Springer, 2014, pp. 247–53, doi:10.1007/s10863-014-9554-z. short: L.A. Sazanov, Journal of Bioenergetics and Biomembranes 46 (2014) 247–253. date_created: 2018-12-11T11:55:01Z date_published: 2014-08-01T00:00:00Z date_updated: 2021-01-12T06:54:28Z day: '01' doi: 10.1007/s10863-014-9554-z extern: 1 intvolume: ' 46' issue: '4' month: '08' page: 247 - 253 publication: Journal of Bioenergetics and Biomembranes publication_status: published publisher: Springer publist_id: '5104' quality_controlled: 0 status: public title: The mechanism of coupling between electron transfer and proton translocation in respiratory complex I type: journal_article volume: 46 year: '2014' ... --- _id: '1989' abstract: - lang: eng text: During animal cell division, the cleavage furrow is positioned by microtubules that signal to the actin cortex at the cell midplane. We developed a cell-free system to recapitulate cytokinesis signaling using cytoplasmic extract from Xenopus eggs. Microtubules grew out as asters from artificial centrosomes and met to organize antiparallel overlap zones. These zones blocked the interpenetration of neighboring asters and recruited cytokinesis midzone proteins, including the chromosomal passenger complex (CPC) and centralspindlin. The CPC was transported to overlap zones, which required two motor proteins, Kif4A and a Kif20A paralog. Using supported lipid bilayers to mimic the plasma membrane, we observed the recruitment of cleavage furrow markers, including an active RhoA reporter, at microtubule overlaps. This system opens further approaches to understanding the biophysics of cytokinesis signaling. acknowledgement: 'This work was supported by NIH grant GM39565 (T.J.M.); MBL fellowships from the Evans Foundation, MBL Associates, and the Colwin Fund (T.J.M. and C.M.F.); HFSP fellowship LT000466/2012-L (M.L.); and NIH grant GM103785 (M.W.). ' author: - first_name: Phuong full_name: Nguyen, Phuong A last_name: Nguyen - first_name: Aaron full_name: Groen, Aaron C last_name: Groen - first_name: Martin full_name: Martin Loose id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 - first_name: Keisuke full_name: 'Ishihara, Keisuke ' last_name: Ishihara - first_name: Martin full_name: 'Wühr, Martin ' last_name: Wühr - first_name: Christine full_name: Field, Christine M last_name: Field - first_name: Timothy full_name: Mitchison, Timothy J last_name: Mitchison citation: ama: Nguyen P, Groen A, Loose M, et al. Spatial organization of cytokinesis signaling reconstituted in a cell-free system. Science. 2014;346(6206):244-247. doi:10.1126/science.1256773 apa: Nguyen, P., Groen, A., Loose, M., Ishihara, K., Wühr, M., Field, C., & Mitchison, T. (2014). Spatial organization of cytokinesis signaling reconstituted in a cell-free system. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1256773 chicago: Nguyen, Phuong, Aaron Groen, Martin Loose, Keisuke Ishihara, Martin Wühr, Christine Field, and Timothy Mitchison. “Spatial Organization of Cytokinesis Signaling Reconstituted in a Cell-Free System.” Science. American Association for the Advancement of Science, 2014. https://doi.org/10.1126/science.1256773. ieee: P. Nguyen et al., “Spatial organization of cytokinesis signaling reconstituted in a cell-free system,” Science, vol. 346, no. 6206. American Association for the Advancement of Science, pp. 244–247, 2014. ista: Nguyen P, Groen A, Loose M, Ishihara K, Wühr M, Field C, Mitchison T. 2014. Spatial organization of cytokinesis signaling reconstituted in a cell-free system. Science. 346(6206), 244–247. mla: Nguyen, Phuong, et al. “Spatial Organization of Cytokinesis Signaling Reconstituted in a Cell-Free System.” Science, vol. 346, no. 6206, American Association for the Advancement of Science, 2014, pp. 244–47, doi:10.1126/science.1256773. short: P. Nguyen, A. Groen, M. Loose, K. Ishihara, M. Wühr, C. Field, T. Mitchison, Science 346 (2014) 244–247. date_created: 2018-12-11T11:55:04Z date_published: 2014-10-10T00:00:00Z date_updated: 2021-01-12T06:54:32Z day: '10' doi: 10.1126/science.1256773 extern: 1 intvolume: ' 346' issue: '6206' month: '10' page: 244 - 247 publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '5093' quality_controlled: 0 status: public title: Spatial organization of cytokinesis signaling reconstituted in a cell-free system type: journal_article volume: 346 year: '2014' ... --- _id: '1990' abstract: - lang: eng text: 'Bacterial cytokinesis is commonly initiated by the Z-ring, a cytoskeletal structure that assembles at the site of division. Its primary component is FtsZ, a tubulin superfamily GTPase, which is recruited to the membrane by the actin-related protein FtsA. Both proteins are required for the formation of the Z-ring, but if and how they influence each other''s assembly dynamics is not known. Here, we reconstituted FtsA-dependent recruitment of FtsZ polymers to supported membranes, where both proteins self-organize into complex patterns, such as fast-moving filament bundles and chirally rotating rings. Using fluorescence microscopy and biochemical perturbations, we found that these large-scale rearrangements of FtsZ emerge from its polymerization dynamics and a dual, antagonistic role of FtsA: recruitment of FtsZ filaments to the membrane and negative regulation of FtsZ organization. Our findings provide a model for the initial steps of bacterial cell division and illustrate how dynamic polymers can self-organize into large-scale structures.' acknowledgement: M.L. is supported by fellowships from EMBO (ALTF 394-2011) and HFSP (LT000466/2012). Cytoskeleton dynamics research in the T.J.M. group is supported by NIH-GM39565. author: - first_name: Martin full_name: Martin Loose id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 - first_name: Timothy full_name: Mitchison, Timothy J last_name: Mitchison citation: ama: Loose M, Mitchison T. The bacterial cell division proteins ftsA and ftsZ self-organize into dynamic cytoskeletal patterns. Nature Cell Biology. 2014;16(1):38-46. doi:10.1038/ncb2885 apa: Loose, M., & Mitchison, T. (2014). The bacterial cell division proteins ftsA and ftsZ self-organize into dynamic cytoskeletal patterns. Nature Cell Biology. Nature Publishing Group. https://doi.org/10.1038/ncb2885 chicago: Loose, Martin, and Timothy Mitchison. “The Bacterial Cell Division Proteins FtsA and FtsZ Self-Organize into Dynamic Cytoskeletal Patterns.” Nature Cell Biology. Nature Publishing Group, 2014. https://doi.org/10.1038/ncb2885. ieee: M. Loose and T. Mitchison, “The bacterial cell division proteins ftsA and ftsZ self-organize into dynamic cytoskeletal patterns,” Nature Cell Biology, vol. 16, no. 1. Nature Publishing Group, pp. 38–46, 2014. ista: Loose M, Mitchison T. 2014. The bacterial cell division proteins ftsA and ftsZ self-organize into dynamic cytoskeletal patterns. Nature Cell Biology. 16(1), 38–46. mla: Loose, Martin, and Timothy Mitchison. “The Bacterial Cell Division Proteins FtsA and FtsZ Self-Organize into Dynamic Cytoskeletal Patterns.” Nature Cell Biology, vol. 16, no. 1, Nature Publishing Group, 2014, pp. 38–46, doi:10.1038/ncb2885. short: M. Loose, T. Mitchison, Nature Cell Biology 16 (2014) 38–46. date_created: 2018-12-11T11:55:05Z date_published: 2014-01-01T00:00:00Z date_updated: 2021-01-12T06:54:33Z day: '01' doi: 10.1038/ncb2885 extern: 1 intvolume: ' 16' issue: '1' month: '01' page: 38 - 46 publication: Nature Cell Biology publication_status: published publisher: Nature Publishing Group publist_id: '5094' quality_controlled: 0 status: public title: The bacterial cell division proteins ftsA and ftsZ self-organize into dynamic cytoskeletal patterns type: journal_article volume: 16 year: '2014' ... --- _id: '1996' abstract: - lang: eng text: Auxin polar transport, local maxima, and gradients have become an importantmodel system for studying self-organization. Auxin distribution is regulated by auxin-dependent positive feedback loops that are not well-understood at the molecular level. Previously, we showed the involvement of the RHO of Plants (ROP) effector INTERACTOR of CONSTITUTIVELY active ROP 1 (ICR1) in regulation of auxin transport and that ICR1 levels are posttranscriptionally repressed at the site of maximum auxin accumulation at the root tip. Here, we show that bimodal regulation of ICR1 levels by auxin is essential for regulating formation of auxin local maxima and gradients. ICR1 levels increase concomitant with increase in auxin response in lateral root primordia, cotyledon tips, and provascular tissues. However, in the embryo hypophysis and root meristem, when auxin exceeds critical levels, ICR1 is rapidly destabilized by an SCF(TIR1/AFB) [SKP, Cullin, F-box (transport inhibitor response 1/auxin signaling F-box protein)]-dependent auxin signaling mechanism. Furthermore, ectopic expression of ICR1 in the embryo hypophysis resulted in reduction of auxin accumulation and concomitant root growth arrest. ICR1 disappeared during root regeneration and lateral root initiation concomitantly with the formation of a local auxin maximum in response to external auxin treatments and transiently after gravitropic stimulation. Destabilization of ICR1 was impaired after inhibition of auxin transport and signaling, proteasome function, and protein synthesis. A mathematical model based on these findings shows that an in vivo-like auxin distribution, rootward auxin flux, and shootward reflux can be simulated without assuming preexisting tissue polarity. Our experimental results and mathematical modeling indicate that regulation of auxin distribution is tightly associated with auxin-dependent ICR1 levels. author: - first_name: Ora full_name: Hazak, Ora last_name: Hazak - first_name: Uri full_name: Obolski, Uri last_name: Obolski - first_name: Tomas full_name: Prat, Tomas id: 3DA3BFEE-F248-11E8-B48F-1D18A9856A87 last_name: Prat - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 - first_name: Lilach full_name: Hadany, Lilach last_name: Hadany - first_name: Shaul full_name: Yalovsky, Shaul last_name: Yalovsky citation: ama: Hazak O, Obolski U, Prat T, Friml J, Hadany L, Yalovsky S. Bimodal regulation of ICR1 levels generates self-organizing auxin distribution. PNAS. 2014;111(50):E5471-E5479. doi:10.1073/pnas.1413918111 apa: Hazak, O., Obolski, U., Prat, T., Friml, J., Hadany, L., & Yalovsky, S. (2014). Bimodal regulation of ICR1 levels generates self-organizing auxin distribution. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1413918111 chicago: Hazak, Ora, Uri Obolski, Tomas Prat, Jiří Friml, Lilach Hadany, and Shaul Yalovsky. “Bimodal Regulation of ICR1 Levels Generates Self-Organizing Auxin Distribution.” PNAS. National Academy of Sciences, 2014. https://doi.org/10.1073/pnas.1413918111. ieee: O. Hazak, U. Obolski, T. Prat, J. Friml, L. Hadany, and S. Yalovsky, “Bimodal regulation of ICR1 levels generates self-organizing auxin distribution,” PNAS, vol. 111, no. 50. National Academy of Sciences, pp. E5471–E5479, 2014. ista: Hazak O, Obolski U, Prat T, Friml J, Hadany L, Yalovsky S. 2014. Bimodal regulation of ICR1 levels generates self-organizing auxin distribution. PNAS. 111(50), E5471–E5479. mla: Hazak, Ora, et al. “Bimodal Regulation of ICR1 Levels Generates Self-Organizing Auxin Distribution.” PNAS, vol. 111, no. 50, National Academy of Sciences, 2014, pp. E5471–79, doi:10.1073/pnas.1413918111. short: O. Hazak, U. Obolski, T. Prat, J. Friml, L. Hadany, S. Yalovsky, PNAS 111 (2014) E5471–E5479. date_created: 2018-12-11T11:55:07Z date_published: 2014-12-16T00:00:00Z date_updated: 2021-01-12T06:54:35Z day: '16' department: - _id: JiFr doi: 10.1073/pnas.1413918111 intvolume: ' 111' issue: '50' language: - iso: eng main_file_link: - open_access: '1' url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273421/ month: '12' oa: 1 oa_version: Submitted Version page: E5471 - E5479 publication: PNAS publication_status: published publisher: National Academy of Sciences publist_id: '5083' quality_controlled: '1' scopus_import: 1 status: public title: Bimodal regulation of ICR1 levels generates self-organizing auxin distribution type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 111 year: '2014' ...