ACS Publications. Most Trusted. Most Cited. Most Read
Solution Conformation of the Antibody-Bound Tyrosine Phosphorylation Site of the Nicotinic Acetylcholine Receptor β-Subunit in Its Phosphorylated and Nonphosphorylated States

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:Biochemistry 2003, 42, 24, 7371-7380
    Article

    Solution Conformation of the Antibody-Bound Tyrosine Phosphorylation Site of the Nicotinic Acetylcholine Receptor β-Subunit in Its Phosphorylated and Nonphosphorylated States†
    Click to copy article linkArticle link copied!

    View Author Information
    Laboratoire de Chimie-Physique Macromoléculaire, UMR 7568 CNRS−INPL, Groupe ENSIC, 1 Rue Grandville, B.P. 451, 54001 Nancy Cedex, France, Department of Chemistry, University of Ioannina, Box 1186, 451 10 Ioannina, Greece, Department of Biochemistry, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 115 21 Athens, Greece, and Department of Pharmacy, University of Patras, 265 04 Patras, Greece
    Other Access OptionsSupporting Information (1)

    Biochemistry

    Cite this: Biochemistry 2003, 42, 24, 7371–7380
    Click to copy citationCitation copied!
    https://doi.org/10.1021/bi030034u
    Published May 30, 2003
    Copyright © 2003 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!

    Phosphorylation of the acetylcholine receptor (AChR) seems to be responsible for triggering several effects including its desensitization and aggregation at the postsynaptic membrane and probably initiates a signal transduction pathway at the postsynaptic membrane. To study the structural and functional role of the tyrosine phosphorylation site of the AChR β-subunit and contribute to the in-depth understanding of the structural basis of the ion channel function, we synthesized four peptides containing the phosphorylated and nonphosphorylated sequences (380−391) of the human and Torpedo AChR β-subunits and studied their interaction with a monoclonal antibody (mAb 148) that is known to bind to this region and that is capable of blocking ion channel function. All four peptides were efficient inhibitors of mAb 148 binding to AChR, although the nonphosphorylated human peptide was considerably less effective than the three others. We then investigated the conformation acquired by all four peptides in their antibody-bound state, which possibly illustrates the local conformation of the corresponding sites on the intact AChR molecule. The phosphorylated human and Torpedo peptides adopted a distorted 310 helix conformation. The nonphosphorylated Torpedo peptide, which is also an efficient inhibitor, was also folded. In contrast, the nonphosphorylated human peptide (a less efficient inhibitor) presented an extended structure. It is concluded that the phosphorylation of the AChR at its β-subunit Tyr site leads to a significant change in its conformation, which may affect several functions of the AChR.

    Copyright © 2003 American Chemical Society

    Subjects

    what are subjects

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    †

     This work was supported by the Association Française contre les Myopathies (AFM), the Biotechnology program of the EU (Grant BIO4-CT98-0110), the Quality of Life program of the EU (Grant QLG3-CT-2001-00902), and the Centre National de la Recherche Scientifique.

    ‡

     Laboratoire de Chimie Physique Macromoléculaire.

    §

     University of Ioannina.

    ‖

     Hellenic Pasteur Institute.

    *

     To whom correspondence should be addressed. (M.T.C) Phone:  (33) 383 175107. Fax:  (33) 383 379977. E-mail:  Manh-Thong.Cung@ ensic.inpl-nancy.fr. (S.J.T.) Phone:  30-210-6478844. Fax:  30-210-6478842. E-mail:  [email protected].

    ⊥

     University of Patras.

    Supporting Information Available

    Click to copy section linkSection link copied!

    Table S1:  Chemical shifts (ppm) of assigned proton resonances of nonphosphorylated and phosphorylated human and Torpedo peptides in the presence of mAb 148 at pH 7 in H2O and D2O (95:5 v/v). This material is available free of charge via the Internet at http://pubs.acs.org.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 11 publications.

    1. Sergio E. Wong,, Katarzyna Bernacki, and, Matthew Jacobson. Competition between Intramolecular Hydrogen Bonds and Solvation in Phosphorylated Peptides:  Simulations with Explicit and Implicit Solvent. The Journal of Physical Chemistry B 2005, 109 (11) , 5249-5258. https://doi.org/10.1021/jp046333q
    2. Josyane Gharbi-Benarous,, Gildas Bertho,, Nathalie Evrard-Todeschi,, Gaël Coadou,, Simon Megy,, Thierry Delaunay,, Richard Benarous, and, Jean-Pierre Girault. Epitope Mapping of the Phosphorylation Motif of the HIV-1 Protein Vpu Bound to the Selective Monoclonal Antibody Using TRNOESY and STD NMR Spectroscopy. Biochemistry 2004, 43 (46) , 14555-14565. https://doi.org/10.1021/bi0492861
    3. Austin T. Weigle, Jiangyan Feng, Diwakar Shukla. Thirty years of molecular dynamics simulations on posttranslational modifications of proteins. Physical Chemistry Chemical Physics 2022, 24 (43) , 26371-26397. https://doi.org/10.1039/D2CP02883B
    4. Philip Seeman. Are dopamine D2 receptors out of control in psychosis?. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2013, 46 , 146-152. https://doi.org/10.1016/j.pnpbp.2013.07.006
    5. Athanassios Stavrakoudis. Cis - trans isomerization of the Epstein-Barr virus determinant peptide EENLLDFVRF after the DM1 TCR recognition of the HLA-B*4405/peptide complex. FEBS Letters 2011, 585 (3) , 485-491. https://doi.org/10.1016/j.febslet.2010.12.013
    6. Lucia S. Borges, Sergey Yechikhov, Young I. Lee, John B. Rudell, Matthew B. Friese, Steven J. Burden, Michael J. Ferns. Identification of a Motif in the Acetylcholine Receptor β Subunit Whose Phosphorylation Regulates Rapsyn Association and Postsynaptic Receptor Localization. The Journal of Neuroscience 2008, 28 (45) , 11468-11476. https://doi.org/10.1523/JNEUROSCI.2508-08.2008
    7. Burkhard Luy, Andreas Frank, Horst Kessler. Conformational Analysis of Drugs by Nuclear Magnetic Resonance Spectroscopy. 2007, 207-254. https://doi.org/10.1002/9783527621286.ch9
    8. Eli S Groban, Arjun Narayanan, Matthew P Jacobson, . Conformational Changes in Protein Loops and Helices Induced by Post-Translational Phosphorylation. PLoS Computational Biology 2006, 2 (4) , e32. https://doi.org/10.1371/journal.pcbi.0020032
    9. Ge Huang, Debin Wang, Liping Guo, Nianxi Zhao, Yuanyuan Li, Shih-Hsin Lu. Monoclonal Antibodies to Esophageal Cancer–Related Gene2 Protein. Hybridoma 2005, 24 (2) , 86-91. https://doi.org/10.1089/hyb.2005.24.86
    10. Denise Kottwitz, Viktoria Kukhtina, Natalia Dergousova, Timophey Alexeev, Yuri Utkin, Victor Tsetlin, Ferdinand Hucho. Intracellular domains of the δ-subunits of Torpedo and rat acetylcholine receptors—expression, purification, and characterization. Protein Expression and Purification 2004, 38 (2) , 237-247. https://doi.org/10.1016/j.pep.2004.07.017
    11. J. Kardos. Chapter 8 Sorption (binding) and transport phenomena in biomembranes. 2004, 215-277. https://doi.org/10.1016/S1573-4285(04)80062-0
    Download PDF
    Go to Biochemistry
    Get e-Alerts
    Get e-Alerts

    Biochemistry

    Cite this: Biochemistry 2003, 42, 24, 7371–7380
    Click to copy citationCitation copied!
    https://doi.org/10.1021/bi030034u
    Published May 30, 2003
    Copyright © 2003 American Chemical Society
    Request reuse permissions

    Article Views

    116

    Altmetric

    -

    Citations

    11
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.