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254 results on '"Haertlein, M."'

7. Strikingly Different Roles of SARS-CoV-2 Fusion Peptides Uncovered by Neutron Scattering

Author

Santamaria, A., Batchu, K.C., Matsarskaia, O., Prévost, S.F., Russo, D., Natali, F., Seydel, T., Hoffmann, I., Laux, V., Haertlein, M., Darwish, T.A., Russell, R.A., Corucci, G., Fragneto, G., Maestro, A., Zaccai Nathan, R., Zaccai, N.R., Science and Technology Facilities Council (UK), Wellcome Trust, Agence Nationale de la Recherche (France), National Science Foundation (US), National Collaborative Research Infrastructure Strategy (Australia), Santamaria, Andreas [0000-0002-6151-4406], Matsarskaia, Olga [0000-0002-7293-7287], Seydel, Tilo [0000-0001-9630-1630], Hoffmann, Ingo [0000-0001-7178-6467], Darwish, Tamim A [0000-0001-7704-1837], Maestro, Armando [0000-0002-7791-8130], Zaccai, Nathan R [0000-0002-1476-2044], Apollo - University of Cambridge Repository, and Zaccai, Nathan [0000-0002-1476-2044]

Subjects
Membrane Fluidity, viruses, Lipid Bilayers, chemistry.chemical_element, Neutron scattering, Calcium, medicine.disease_cause, Biochemistry, Catalysis, Colloid and Surface Chemistry, Protein Domains, Scattering, Small Angle, medicine, Amino Acid Sequence, Unilamellar Liposomes, Coronavirus, Fusion, Chemistry, SARS-CoV-2, Lipid bilayer fusion, General Chemistry, Small-angle neutron scattering, Peptide Fragments, Neutron Diffraction, Membrane, Cholesterol, Spike Glycoprotein, Coronavirus, Biophysics, Neutron reflectometry
Abstract

Funder: National Collaborative Research Infrastructure Strategy (NCRIS), Funder: ANR/NSF-PIRE, Funder: Science and Technology Facilities Council, Funder: Institut Laue Langevin, Coronavirus disease-2019 (COVID-19), a potentially lethal respiratory illness caused by the coronavirus SARS-CoV-2, emerged in the end of 2019 and has since spread aggressively across the globe. A thorough understanding of the molecular mechanisms of cellular infection by coronaviruses is therefore of utmost importance. A critical stage in infection is the fusion between viral and host membranes. Here, we present a detailed investigation of the role of selected SARS-CoV-2 Spike fusion peptides, and the influence of calcium and cholesterol, in this fusion process. Structural information from specular neutron reflectometry and small angle neutron scattering, complemented by dynamics information from quasi-elastic and spin-echo neutron spectroscopy, revealed strikingly different functions encoded in the Spike fusion domain. Calcium drives the N-terminal of the Spike fusion domain to fully cross the host plasma membrane. Removing calcium, however, reorients the peptide back to the lipid leaflet closest to the virus, leading to significant changes in lipid fluidity and rigidity. In conjunction with other regions of the fusion domain, which are also positioned to bridge and dehydrate viral and host membranes, the molecular events leading to cell entry by SARS-CoV-2 are proposed.

Published
2022

14. New sources and instrumentation for neutrons in biology

Author

Teixeira, S.C.M., Zaccai, G., Ankner, J., Bellissent-Funel, M.C., Bewley, R., Blakeley, M.P., Callow, P., Coates, L., Dahint, R., Dalgliesh, R., Dencher, N.A., Forsyth, V.T., Fragneto, G., Frick, B., Gilles, R., Gutberlet, T., Haertlein, M., Hauß, T., Häußler, W., Heller, W.T., Herwig, K., Holderer, O., Juranyi, F., Kampmann, R., Knott, R., Krueger, S., Langan, P., Lechner, R.E., Lynn, G., Majkrzak, C., May, R.P., Meilleur, F., Mo, Y., Mortensen, K., Myles, D.A.A., Natali, F., Neylon, C., Niimura, N., Ollivier, J., Ostermann, A., Peters, J., Pieper, J., Rühm, A., Schwahn, D., Shibata, K., Soper, A.K., Strässle, Th., Suzuki, J., Tanaka, I., Tehei, M., Timmins, P., Torikai, N., Unruh, T., Urban, V., Vavrin, R., and Weiss, K.

Published
2008
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26. Neutron radiobiology studies with a pure cold neutron beam: application to the measurement of the thermal neutron RBE of A375 melanoma cells for Boron Neutron Capture Therapy

Author

Pedrosa-Rivera, María, Ruiz-Magaña, María José, Porras Sánchez, José Ignacio, Praena Rodríguez, Antonio Javier, Torres Sánchez, Pablo, Sabariego Quintanilla, Manuel, Köster, U., Forsyth, T., Soldner, T., Haertlein, M., and Ruiz Ruiz, María Carmen

Subjects
Boron neutron capture therapy, Neutron radiobiology, Astrophysics::High Energy Astrophysical Phenomena, Nuclear Theory, Physics::Medical Physics, Nuclear Experiment, Neutron sources
Abstract

Data on the radiobiological effects of thermal neutrons are usually obtained from irradiations in a mixed field of neutrons of different energies and gamma rays or from conversion of proton data with similar energies to those created in the neutron capture on nitrogen. Experimental data from irradiations in a pure thermal or cold neutron beam can help to find new values for neutron relative biological effectiveness (RBE) factors, which are useful for BNCT (Boron Neutron Capture Therapy) and radiation protection applications. We present a new experimental setup for radiobiological studies at a cold neutron beam at Institut Laue-Langevin, a beam without fast neutron component and almost no gamma ray contribution. After the irradiation, survival assays are performed to obtain the survival curves. Finally, comparing with a reference photon irradiation, the thermal neutron RBE factors can be calculated. The methodology is outlined at the example of A375 melanoma cells for which new radiobiological data were obtained., Institut Laue-Langevin, Avenue des Martyrs, 38042 Grenoble, France. Departamento de Física Atómica Molecular y Nuclear, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain. Departamento de Bioquímica y Biología Molecular III e Inmunología, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain., We acknowledge financial support for this work from the Fundación Científica de la Asociación Española Contra el Cáncer (AECC) under grant PS16163811PORR, Junta de Andalucía (Andalusian Regional Government), under contract P11-FQM-8229, Spanish MINECO and FEDER funds under contract FIS2015-69941-C2-1-P, and the founders of the University of Granada Chair Neutrons for Medicine: Spanish Fundación ACS and Capitán Antonio. M.P. acknowledges a grant under the program Becas de Iniciación a la Investigación from the Universidad de Granada (Plan Propio de Investigación).

Published
2019

27. Moringa seed protein Mo-CBP3-4

Author

Moulin, M., primary, Mossou, E., additional, Mitchell, E.P., additional, Haertlein, M., additional, Forsyth, V.T., additional, and Rennie, A.R., additional

Published
2019
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28. Dynamic self-assembly of DNA minor groove-binding ligand DB921 into nanotubes triggered by an alkali halide

Author

Mizuta, R., Devos, J.M., Webster, J., Ling, W.L., Narayanan, T., Round, A., Munnur, D., Mossou, E., Farahat, A.A., Boykin, D.W., Wilson, W.D., Neidle, S., Schweins, R., Rannou, P., Haertlein, M., Forsyth, V.T., Mitchell, E.P., European Synchrotron Radiation Facility (ESRF), European Molecular Biology Laboratory [Grenoble] (EMBL), Inst Max Von Laue Paul Langevin, F-38042 Grenoble, France, Institut Laue-Langevin (ILL), ILL, SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ILL-EMBL, and Swiss Federal Research Institute

Subjects
[PHYS]Physics [physics], [CHIM.POLY]Chemical Sciences/Polymers, [CHIM]Chemical Sciences, QD, [CHIM.MATE]Chemical Sciences/Material chemistry, [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, ComputingMilieux_MISCELLANEOUS
Abstract

We describe a novel self-assembling supramolecular nanotube system formed by a heterocyclic cationic molecule which was originally designed for its potential as an antiparasitic and DNA sequence recognition agent. Our structural characterisation work indicates that the nanotubes form via a hierarchical assembly mechanism that can be triggered and tuned by well-defined concentrations of simple alkali halide salts in water. The nanotubes assembled in NaCl have inner and outer diameters of ca. 22 nm and 26 nm respectively, with lengths that reach into several microns. Our results suggest the tubes consist of DB921 molecules stacked along the direction of the nanotube long axis. The tubes are stabilised by face-to-face π–π stacking and ionic interactions between the charged amidinium groups of the ligand and the negative halide ions. The assembly process of the nanotubes was followed using small-angle X-ray and neutron scattering, transmission electron microscopy and ultraviolet/visible spectroscopy. Our data demonstrate that assembly occurs through the formation of intermediate ribbon-like structures that in turn form helices that tighten and compact to form the final stable filament. This assembly process was tested using different alkali–metal salts, showing a strong preference for chloride or bromide anions and with little dependency on the type of cation. Our data further demonstrates the existence of a critical anion concentration above which the rate of self-assembly is greatly enhanced.

Published
2018
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34. Deuterium effects on human serum albumin in solution

Author

White, John, Laux, Valerie, Fraser, Nicholas, Heß, David, Haertlein, M., Forsyth, Trevor, White, John, Laux, Valerie, Fraser, Nicholas, Heß, David, Haertlein, M., and Forsyth, Trevor

Abstract

We report the thermodynamic effects of heavy water and intra- molecular deuteration on the melting and aggregation of fatted and defatted human serum albumin (FHSA and DFHSA) in 250 mM salt. Eight different combinations with and without deuterium were produced by recombinant expression of the proteins in the yeast Pichia pastoris. Human serum albumin is 47% of the protein in blood and is an important carrier of fat and medicines throughout the body. It is a potential carrier of invasive nanoparticles. The x-ray crystal structures of the molecule in its native and recombinant forms, with and without the fat molecule, and with drug molecules have been determined to 1.8 Å resolution by x-ray diffraction [1–3]. The structures of the fatted and defatted molecules in this 67kD molecule are very similar and the local conformational changes associated with the fat ligand as well as drug molecules are established. It is well known that the structures of fully deuterated proteins and their hydrogenous counterparts are closely similar [4–7] and so it was a surprise, in 2013, that strong aggregation of a fully deuterated sample of human serum albumin in heavy water buffer was found at the outset of a neutron experiment to study the protein corona around silica nano

Published
2018

45. Crowding of membrane proteins and peptides

Author

Grage, S, Afonin, S, Wadhwani, P, Mykhailiuk, P, Berditsch, M, Turdzeladze, T, May, R, Haertlein, M, Callow, P, Watts, A, Huang, K, Martinac, B, and Ulrich, A

Published
2011

47. High-resolution neutron and X-ray diffraction room-temperature studies of an H-FABP–oleic acid complex: study of the internal water cluster and ligand binding by a transferred multipolar electron-density distribution

Author

Howard, E. I., primary, Guillot, B., additional, Blakeley, M. P., additional, Haertlein, M., additional, Moulin, M., additional, Mitschler, A., additional, Cousido-Siah, A., additional, Fadel, F., additional, Valsecchi, W. M., additional, Tomizaki, Takashi, additional, Petrova, T., additional, Claudot, J., additional, and Podjarny, A., additional

Published
2016
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48. The aggregation of 'native' human serum albumin

Author

White, John, Hess (Heß), David, Raynes, J. K., Laux, Valerie, Haertlein, M., Forsyth, Trevor, Jeyasingham, Anithahini, White, John, Hess (Heß), David, Raynes, J. K., Laux, Valerie, Haertlein, M., Forsyth, Trevor, and Jeyasingham, Anithahini

Abstract

Recombinant fully deuterated, defatted human serum albumin in heavy water was found to be about 90 % aggregated before final fractionation. For comparison and to establish a datum for this isotope effect, the extent of aggregation is reported for “nati

Published
2015

49. Lipid polyunsaturation determines the extent of membrane structural changes induced by Amphotericin B in Pichia pastoris yeast

Author

De Ghellinck D'Elseghem, Alexis, V, Laux, Haertlein, M, Jouhet, J, Sferrazza, Michele, Wacklin, H., De Ghellinck D'Elseghem, Alexis, V, Laux, Haertlein, M, Jouhet, J, Sferrazza, Michele, and Wacklin, H.

Abstract

The activity of the potent but highly toxic antifungal drug Amphotericin B (AmB), used intravenously to treat systemic fungal and parasitic infections, is widely accepted to result from its specific interaction with the fungal sterol ergosterol. While the effect of sterols on AmB activity has been intensely investigated, the role of membrane phospholipid composition has largely been ignored, and structural studies of native membranes have been hampered by their complex and disordered nature. We show for the first time that the structure of fungal membranes derived from Pichia pastoris yeast depends on the degree of lipid polyunsaturation, which has an impact on the structural consequences of AmB activity. AmB inserts in yeast membranes even in the absence of ergosterol, and forms an extra-membraneous layer whose thickness is resolved to be 4-5 nm. In ergosterol-containing membranes, AmB insertion is accompanied by ergosterol extraction into this layer. The AmB-sponge mediated depletion of ergosterol from P. pastoris membranes gives rise to a significant membrane thinning effect that depends on the degree of lipid polyunsaturation. The resulting hydrophobic mismatch is likely to interfere with a much broader range of membrane protein functions than those directly involving ergosterol, and suggests that polyunsaturated lipids could boost the efficiency of AmB. Furthermore, a low degree of lipid polyunsaturation leads to least AmB insertion and may protect host cells against the toxic effects of AmB. These results provide a new framework based on lipid composition and membrane structure through which we can understand its antifungal action and develop better treatments., info:eu-repo/semantics/published

Published
2015

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