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Metaphosphate Stabilization in the Myosin ATPase [Enzymology] (2013)

Kiani, F. A., Fischer, S.

The American Society for Biochemistry and Molecular Biology (ASBMB)

In: Journal of Biological Chemistry

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Publication Date: 2013-12-07

Description: It has been proposed recently that ATP hydrolysis in ATPase enzymes proceeds via an initial intermediate in which the dissociated γ-phosphate of ATP is bound in the protein as a metaphosphate (PγO3−). A combined quantum/classical analysis of this dissociated nucleotide state inside myosin provides a quantitative understanding of how the enzyme stabilizes this unusual metaphosphate. Indeed, in vacuum, the energy of the ADP3−·PγO3−·Mg2+ complex is much higher than that of the undissociated ATP4−. The protein brings it to a surprisingly low value. Energy decomposition reveals how much each interaction in the protein stabilizes the metaphosphate state; backbone peptides of the P-loop contribute 50% of the stabilization energy, and the side chain of Lys-185+ contributes 25%. This can be explained by the fact that these groups make strong favorable interactions with the α- and β-phosphates, thus favoring the charge distribution of the metaphosphate state over that of the ATP state. Further stabilization (16%) is achieved by a hydrogen bond between the backbone C=O of Ser-237 (on loop Switch-1) and a water molecule perfectly positioned to attack the PγO3− in the subsequent hydrolysis step. The planar and singly negative PγO3− is a much better target for the subsequent nucleophilic attack by a negatively charged OH− than the tetrahedral and doubly negative PγO42− group of ATP. Therefore, we argue that the present mechanism of metaphosphate stabilization is common to the large family of nucleotide-hydrolyzing enzymes. Methodologically, this work presents a computational approach that allows us to obtain a truly quantitative conception of enzymatic strategy.

Print ISSN: 0021-9258

Electronic ISSN: 1083-351X

Topics: Biology , Chemistry and Pharmacology

Published by The American Society for Biochemistry and Molecular Biology (ASBMB)

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The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory cytopenia of childhood: a prospective study by EWOG-MDS (2014)

A M Aalbers; V H J van der Velden; A Yoshimi; A Fischer; P Noellke; C M Zwaan; I Baumann; H B Beverloo; M Dworzak; H Hasle; F Locatelli; B De Moerloose; G Göhring; M Schmugge; J Stary; M Zecca; A W Langerak; J J M van Dongen; R Pieters; C M Niemeyer; M M van den Heuvel-Eibrink

Nature Publishing Group (NPG)

In: Leukemia

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Publication Date: 2014-01-09

Description: The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory cytopenia of childhood: a prospective study by EWOG-MDS Leukemia 28, 189 (January 2014). doi:10.1038/leu.2013.195 Authors: A M Aalbers, V H J van der Velden, A Yoshimi, A Fischer, P Noellke, C M Zwaan, I Baumann, H B Beverloo, M Dworzak, H Hasle, F Locatelli, B De Moerloose, G Göhring, M Schmugge, J Stary, M Zecca, A W Langerak, J J M van Dongen, R Pieters, C M Niemeyer & M M van den Heuvel-Eibrink

Print ISSN: 0887-6924

Electronic ISSN: 1476-5551

Topics: Medicine

Published by Nature Publishing Group (NPG)

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Self-homodyne measurement of a dynamic Mollow triplet in the solid state (2016)

Kevin A. Fischer; Kai Müller; Armand Rundquist; Tomas Sarmiento; Alexander Y. Piggott; Yousif Kelaita; Constantin Dory; Konstantinos G. Lagoudakis; Jelena Vučković

Nature Publishing Group (NPG)

In: Nature Photonics

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Publication Date: 2016-02-27

Description: Nature Photonics 10, 163 (2016). doi:10.1038/nphoton.2015.276 Authors: Kevin A. Fischer, Kai Müller, Armand Rundquist, Tomas Sarmiento, Alexander Y. Piggott, Yousif Kelaita, Constantin Dory, Konstantinos G. Lagoudakis & Jelena Vučković The study of the light–matter interaction at the quantum scale has been enabled by the cavity quantum electrodynamics (CQED) architecture, in which a quantum two-level system strongly couples to a single cavity mode. Originally implemented with atoms in optical cavities, CQED effects are now also observed with artificial atoms in solid-state environments. Such realizations of these systems exhibit fast dynamics, making them attractive candidates for devices including modulators and sources in high-throughput communications. However, these systems possess large photon out-coupling rates that obscure any quantum behaviour at large excitation powers. Here, we have used a self-homodyning interferometric technique that fully employs the complex mode structure of our nanofabricated cavity to observe a quantum phenomenon known as the dynamic Mollow triplet. We expect this interference to facilitate the development of arbitrary on-chip quantum state generators, thereby strongly influencing quantum lithography, metrology and imaging.

Print ISSN: 1749-4885

Electronic ISSN: 1749-4893

Topics: Physics

Published by Nature Publishing Group (NPG)

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Coherent control with a short-wavelength free-electron laser (2016)

K. C. Prince; E. Allaria; C. Callegari; R. Cucini; G. De Ninno; S. Di Mitri; B. Diviacco; E. Ferrari; P. Finetti; D. Gauthier; L. Giannessi; N. Mahne; G. Penco; O. Plekan; L. Raimondi; P. Rebernik; E. Roussel; C. Svetina; M. TrovòM. Zangrando; M. Negro; P. Carpeggiani; M. Reduzzi; G. Sansone; A. N. Grum-Grzhimailo; E. V. Gryzlova; S. I. Strakhova; K. Bartschat; N. Douguet; J. Venzke; D. Iablonskyi; Y. Kumagai; T. Takanashi; K. Ueda; A. Fischer; M. Coreno; F. Stienkemeier; Y. Ovcharenko; T. Mazza; M. Meyer

Nature Publishing Group (NPG)

In: Nature Photonics

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Publication Date: 2016-02-27

Description: Nature Photonics 10, 176 (2016). doi:10.1038/nphoton.2016.13 Authors: K. C. Prince, E. Allaria, C. Callegari, R. Cucini, G. De Ninno, S. Di Mitri, B. Diviacco, E. Ferrari, P. Finetti, D. Gauthier, L. Giannessi, N. Mahne, G. Penco, O. Plekan, L. Raimondi, P. Rebernik, E. Roussel, C. Svetina, M. Trovò, M. Zangrando, M. Negro, P. Carpeggiani, M. Reduzzi, G. Sansone, A. N. Grum-Grzhimailo, E. V. Gryzlova, S. I. Strakhova, K. Bartschat, N. Douguet, J. Venzke, D. Iablonskyi, Y. Kumagai, T. Takanashi, K. Ueda, A. Fischer, M. Coreno, F. Stienkemeier, Y. Ovcharenko, T. Mazza & M. Meyer Extreme ultraviolet and X-ray free-electron lasers (FELs) produce short-wavelength pulses with high intensity, ultrashort duration, well-defined polarization and transverse coherence, and have been utilized for many experiments previously possible only at long wavelengths: multiphoton ionization, pumping an atomic laser and four-wave mixing spectroscopy. However one important optical technique, coherent control, has not yet been demonstrated, because self-amplified spontaneous emission FELs have limited longitudinal coherence. Single-colour pulses from the FERMI seeded FEL are longitudinally coherent, and two-colour emission is predicted to be coherent. Here, we demonstrate the phase correlation of two colours, and manipulate it to control an experiment. Light of wavelengths 63.0 and 31.5 nm ionized neon, and we controlled the asymmetry of the photoelectron angular distribution by adjusting the phase, with a temporal resolution of 3 as. This opens the door to new short-wavelength coherent control experiments with ultrahigh time resolution and chemical sensitivity.

Print ISSN: 1749-4885

Electronic ISSN: 1749-4893

Topics: Physics

Published by Nature Publishing Group (NPG)

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Yap Localization during Mechanosensing Requires Filamentous Actin [Cell Biology] (2016)

Das, A., Fischer, R. S., Pan, D., Waterman, C. M.

The American Society for Biochemistry and Molecular Biology (ASBMB)

In: Journal of Biological Chemistry

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Publication Date: 2016-03-19

Description: Cell-cell contact inhibition and the mechanical environment of cells have both been shown to regulate YAP nuclear localization to modulate cell proliferation. Changes in cellular contractility by genetic, pharmacological, and matrix stiffness perturbations regulate YAP nuclear localization. However, because contractility and F-actin organization are interconnected cytoskeletal properties, it remains unclear which of these distinctly regulates YAP localization. Here we show that in the absence of cell-cell contact, actomyosin contractility suppresses YAP phosphorylation at Ser112, however, neither loss of contractility nor increase in YAP phosphorylation is sufficient for its nuclear exclusion. We find that actin cytoskeletal integrity is essential for YAP nuclear localization, and can override phosphoregulation or contractility-mediated regulation of YAP nuclear localization. This actin-mediated regulation is conserved during mechanotransduction, as substrate compliance increased YAP phosphorylation and reduced cytoskeletal integrity leading to nuclear exclusion of both YAP and Ser(P)112-YAP. These data provide evidence for two actin-mediated pathways for YAP regulation; one in which actomyosin contractility regulates YAP phosphorylation, and a second that involves cytoskeletal integrity-mediated regulation of YAP nuclear localization independent of contractility. We suggest that in non-contact inhibited cells, this latter mechanism may be important in low stiffness regimes, such as may be encountered in physiological environments.

Print ISSN: 0021-9258

Electronic ISSN: 1083-351X

Topics: Biology , Chemistry and Pharmacology

Published by The American Society for Biochemistry and Molecular Biology (ASBMB)

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Mapping polaronic states and lithiation gradients in individual V2O5 nanowires (2016)

Luis R. De Jesus; Gregory A. Horrocks; Yufeng Liang; Abhishek Parija; Cherno Jaye; Linda Wangoh; Jian Wang; Daniel A. Fischer; Louis F. J. Piper; David Prendergast; Sarbajit Banerjee

Nature Publishing Group (NPG)

In: Nature Communications

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Publication Date: 2016-06-30

Description: Article Rapid insertion and extraction of lithium ions from a cathode material is imperative for lithium-ion battery function. Here, the authors present evidence of inhomogeneities in charge localization, local structural distortions and polaron formation induced upon lithiation using scanning transmission X-ray microscopy. Nature Communications doi: 10.1038/ncomms12022 Authors: Luis R. De Jesus, Gregory A. Horrocks, Yufeng Liang, Abhishek Parija, Cherno Jaye, Linda Wangoh, Jian Wang, Daniel A. Fischer, Louis F. J. Piper, David Prendergast, Sarbajit Banerjee

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

Published by Nature Publishing Group (NPG)

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Lymphopoiesis in transgenic mice over-expressing Artemis (2016)

P Rivera-Munoz; V Abramowski; S Jacquot; P AndréS Charrier; K Lipson-Ruffert; A Fischer; A Galy; M Cavazzana; J-P de Villartay

Nature Publishing Group (NPG)

In: Gene Therapy

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Publication Date: 2016-02-05

Description: Lymphopoiesis in transgenic mice over-expressing Artemis Gene Therapy 23, 176 (February 2016). doi:10.1038/gt.2015.95 Authors: P Rivera-Munoz, V Abramowski, S Jacquot, P André, S Charrier, K Lipson-Ruffert, A Fischer, A Galy, M Cavazzana & J-P de Villartay

Print ISSN: 0969-7128

Electronic ISSN: 1476-5462

Topics: Biology , Medicine

Published by Nature Publishing Group (NPG)

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AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages (2015)

E Six; C Lagresle-Peyrou; S Susini; C De Chappedelaine; N Sigrist; H Sadek; M Chouteau; N Cagnard; M Fontenay; O Hermine; C Chomienne; P Reynier; A Fischer; I André-Schmutz; N Gueguen; M Cavazzana

Nature Publishing Group (NPG)

In: Cell Death & Disease

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Publication Date: 2015-08-14

Description: AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages Cell Death and Disease 6, e1856 (August 2015). doi:10.1038/cddis.2015.211 Authors: E Six, C Lagresle-Peyrou, S Susini, C De Chappedelaine, N Sigrist, H Sadek, M Chouteau, N Cagnard, M Fontenay, O Hermine, C Chomienne, P Reynier, A Fischer, I André-Schmutz, N Gueguen & M Cavazzana

Electronic ISSN: 2041-4889

Topics: Biology , Medicine

Published by Nature Publishing Group (NPG)

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Characterization of the CagA-CagF Interaction [Molecular Biophysics] (2013)

Bonsor, D. A., Weiss, E., Iosub-Amir, A., Reingewertz, T. H., Chen, T. W., Haas, R., Friedler, A., Fischer, W., Sundberg, E. J.

The American Society for Biochemistry and Molecular Biology (ASBMB)

In: Journal of Biological Chemistry

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Publication Date: 2013-11-16

Description: CagA is a virulence factor that Helicobacter pylori inject into gastric epithelial cells through a type IV secretion system where it can cause gastric adenocarcinoma. Translocation is dependent on the presence of secretion signals found in both the N- and C-terminal domains of CagA and an interaction with the accessory protein CagF. However, the molecular basis of this essential protein-protein interaction is not fully understood. Herein we report, using isothermal titration calorimetry, that CagA forms a 1:1 complex with a monomer of CagF with nm affinity. Peptide arrays and isothermal titration calorimetry both show that CagF binds to all five domains of CagA, each with μm affinity. More specifically, a coiled coil domain and a C-terminal helix within CagF contacts domains II-III and domain IV of CagA, respectively. In vivo complementation assays of H. pylori with a double mutant, L36A/I39A, in the coiled coil region of CagF showed a severe weakening of the CagA-CagF interaction to such an extent that it was nearly undetectable. However, it had no apparent effect on CagA translocation. Deletion of the C-terminal helix of CagF also weakened the interaction with CagA but likewise had no effect on translocation. These results indicate that the CagA-CagF interface is distributed broadly across the molecular surfaces of these two proteins to provide maximal protection of the highly labile effector protein CagA.

Print ISSN: 0021-9258

Electronic ISSN: 1083-351X

Topics: Biology , Chemistry and Pharmacology

Published by The American Society for Biochemistry and Molecular Biology (ASBMB)

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T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS (2014)

A M Aalbers; M M van den Heuvel-Eibrink; I Baumann; H B Beverloo; G J Driessen; M Dworzak; A Fischer; G Göhring; H Hasle; F Locatelli; B De Moerloose; P Noellke; M Schmugge; J Stary; A Yoshimi; M Zecca; C M Zwaan; J J M van Dongen; R Pieters; C M Niemeyer; V H J van der Velden; A W Langerak

Nature Publishing Group (NPG)

In: Blood Cancer Journal

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Publication Date: 2014-05-03

Description: T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS Blood Cancer Journal 4, e209 (May 2014). doi:10.1038/bcj.2014.28 Authors: A M Aalbers, M M van den Heuvel-Eibrink, I Baumann, H B Beverloo, G J Driessen, M Dworzak, A Fischer, G Göhring, H Hasle, F Locatelli, B De Moerloose, P Noellke, M Schmugge, J Stary, A Yoshimi, M Zecca, C M Zwaan, J J M van Dongen, R Pieters, C M Niemeyer, V H J van der Velden & A W Langerak

Electronic ISSN: 2044-5385

Topics: Medicine

Published by Nature Publishing Group (NPG)

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