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Dynamics of Apolipoprotein B-100 in Interaction with Detergent Probed by Incoherent Neutron Scattering

  • Aline Cisse
    Aline Cisse
    Université Grenoble Alpes, CNRS, LiPhy, 38000 Grenoble, France
    Institut Laue Langevin, 38042 Grenoble, France
    More by Aline Cisse
  • Anna-Laurence Schachner-Nedherer
    Anna-Laurence Schachner-Nedherer
    Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics Division, Medical University of Graz, 8010 Graz, Austria
  • Markus Appel
    Markus Appel
    Institut Laue Langevin, 38042 Grenoble, France
    More by Markus Appel
  • Christian Beck
    Christian Beck
    Institut Laue Langevin, 38042 Grenoble, France
    Institut of Applied Physics, University of Tübingen, 72076 Tübingen, Germany
  • Jacques Ollivier
    Jacques Ollivier
    Institut Laue Langevin, 38042 Grenoble, France
  • Gerd Leitinger
    Gerd Leitinger
    Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Division of Cell Biology, Histology and Embryology, Medical University of Graz, 8010 Graz, Austria
  • Ruth Prassl
    Ruth Prassl
    Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics Division, Medical University of Graz, 8010 Graz, Austria
    More by Ruth Prassl
  • Karin Kornmueller*
    Karin Kornmueller
    Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Biophysics Division, Medical University of Graz, 8010 Graz, Austria
    *Email: [email protected]. Phone: +43 (0) 316 385 71695.
  • , and 
  • Judith Peters*
    Judith Peters
    Université Grenoble Alpes, CNRS, LiPhy, 38000 Grenoble, France
    Institut Laue Langevin, 38042 Grenoble, France
    Institut Universitaire de France, 75231 Paris, France
    *Email: [email protected]. Phone: +33 (0)4 76 20 75 60.
Cite this: J. Phys. Chem. Lett. 2021, 12, 51, 12402–12410
Publication Date (Web):December 23, 2021
https://doi.org/10.1021/acs.jpclett.1c03141
Copyright © 2021 American Chemical Society

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    Abstract

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    Apolipoprotein B-100 (apo B-100) is the protein moiety of both low- and very-low-density lipoproteins, whose role is crucial to cholesterol and triglyceride transport. Aiming at the molecular dynamics’ details of apo B-100, scarcely studied, we performed elastic and quasi-elastic incoherent neutron scattering (EINS, QENS) experiments combining different instruments and time scales. Similar to classical membrane proteins, the solubilization results in remaining detergent, here Nonidet P-40 (NP40). Therefore, we propose a framework for QENS studies of protein–detergent complexes, with the introduction of a combined model, including the experimental apo B-100/NP40 ratio. Relying on the simultaneous analysis of all QENS amplitudes, this approach is sensitive enough to separate both contributions. Its application identified two points: (i) apo B-100 slow dynamics and (ii) the acceleration of NP40 dynamics in the presence of apo B-100. Direct translation of the exposed methodology now makes the investigation of more membrane proteins by neutron spectroscopy achievable.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jpclett.1c03141.

    • Experimental details of the apo B-100 preparation; DSC thermogram of LDL; chemical composition and phase-transition temperatures of each LDL preparation; a chromatogram of six individual SEC runs of one LDL preparation; parameters for determining the detergent contribution; relevant constants for separating protein, detergent, and buffer contributions; apo B-100 lyophilization; the total number of hydrogens in the protein and detergent fractions. Mathematical expressions and details of the QENS model, fitting of the spectra, and Bayesian analyses for different n values. Mathematical expressions and details of the building of the combined model for the amplitudes and global fit of the amplitudes using the combined model for all instruments and samples and for different n values. Mathematical expressions for the linewidths analyses, comparison of the linewidths of the different contributions in each instrument, and summary of the fitting of all line widths as a function of Q2. Additional details of EINS analysis, equation used for the Gaussian approximation, and a comparison between the MSDs of apo B-100 and NP40. Structural information on pure NP40 and apo B-100/NP40 with curves and distance distribution functions from SAXS and SANS.

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    Cited By

    This article is cited by 8 publications.

    1. Valeria Conti Nibali, Alessandro Paciaroni. Virtual Issue on Fast Dynamics and Function of Biomolecules. The Journal of Physical Chemistry Letters 2023, 14 (20) , 4786-4788. https://doi.org/10.1021/acs.jpclett.3c01122
    2. Christian Beck, Marco Grimaldo, Hender Lopez, Stefano Da Vela, Benedikt Sohmen, Fajun Zhang, Martin Oettel, Jean-Louis Barrat, Felix Roosen-Runge, Frank Schreiber, Tilo Seydel. Short-Time Transport Properties of Bidisperse Suspensions of Immunoglobulins and Serum Albumins Consistent with a Colloid Physics Picture. The Journal of Physical Chemistry B 2022, 126 (38) , 7400-7408. https://doi.org/10.1021/acs.jpcb.2c02380
    3. Tatsuhito Matsuo and, Judith Peters. Introduction to Incoherent Neutron Scattering. 2022, 39-68. https://doi.org/10.1002/9781119886358.ch2
    4. Weishu Zhao, Bozitao Zhong, Lirong Zheng, Pan Tan, Yinzhao Wang, Hao Leng, Nicolas de Souza, Zhuo Liu, Liang Hong, Xiang Xiao. Proteome-wide 3D structure prediction provides insights into the ancestral metabolism of ancient archaea and bacteria. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-35523-8
    5. Aline Cisse, Tatsuhito Matsuo, Marie Plazanet, Francesca Natali, Michael Marek Koza, Jacques Ollivier, Dominique J. Bicout, Judith Peters. The dynamical Matryoshka model: 2. Modeling of local lipid dynamics at the sub-nanosecond timescale in phospholipid membranes. Biochimica et Biophysica Acta (BBA) - Biomembranes 2022, 1864 (9) , 183950. https://doi.org/10.1016/j.bbamem.2022.183950
    6. Tatsuhito Matsuo, Judith Peters. Sub-Nanosecond Dynamics of Pathologically Relevant Bio-Macromolecules Observed by Incoherent Neutron Scattering. Life 2022, 12 (8) , 1259. https://doi.org/10.3390/life12081259
    7. Christian Beck, Kevin Pounot, Ilaria Mosca, Niina H Jalarvo, Felix Roosen-Runge, Frank Schreiber, Tilo Seydel, , . Notes on Fitting and Analysis Frameworks for QENS Spectra of (Soft) Colloid Suspensions. EPJ Web of Conferences 2022, 272 , 01004. https://doi.org/10.1051/epjconf/202227201004
    8. Eugene Mamontov, Heloisa N. Bordallo, Olivier Delaire, Jonathan Nickels, Judith Peters, Gerald J. Schneider, Jeremy C. Smith, Alexei P. Sokolov, , . Broadband Wide-Angle VElocity Selector (BWAVES) neutron spectrometer designed for the SNS Second Target Station. EPJ Web of Conferences 2022, 272 , 02003. https://doi.org/10.1051/epjconf/202227202003

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