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Structures of highly flexible intracellular domain of human α7 nicotinic acetylcholine receptor

Author

Listed:
  • Vasyl Bondarenko

    (University of Pittsburgh)

  • Marta M. Wells

    (University of Pittsburgh)

  • Qiang Chen

    (University of Pittsburgh)

  • Tommy S. Tillman

    (University of Pittsburgh)

  • Kevin Singewald

    (University of Pittsburgh)

  • Matthew J. Lawless

    (University of Pittsburgh)

  • Joel Caporoso

    (University of Pittsburgh)

  • Nicole Brandon

    (University of Pittsburgh)

  • Jonathan A. Coleman

    (University of Pittsburgh)

  • Sunil Saxena

    (University of Pittsburgh)

  • Erik Lindahl

    (Stockholm University
    KTH Royal Institute of Technology)

  • Yan Xu

    (University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh)

  • Pei Tang

    (University of Pittsburgh
    University of Pittsburgh
    University of Pittsburgh)

Abstract

The intracellular domain (ICD) of Cys-loop receptors mediates diverse functions. To date, no structure of a full-length ICD is available due to challenges stemming from its dynamic nature. Here, combining nuclear magnetic resonance (NMR) and electron spin resonance experiments with Rosetta computations, we determine full-length ICD structures of the human α7 nicotinic acetylcholine receptor in a resting state. We show that ~57% of the ICD residues are in highly flexible regions, primarily in a large loop (loop L) with the most mobile segment spanning ~50 Å from the central channel axis. Loop L is anchored onto the MA helix and virtually forms two smaller loops, thereby increasing its stability. Previously known motifs for cytoplasmic binding, regulation, and signaling are found in both the helices and disordered flexible regions, supporting the essential role of the ICD conformational plasticity in orchestrating a broad range of biological processes.

Suggested Citation

  • Vasyl Bondarenko & Marta M. Wells & Qiang Chen & Tommy S. Tillman & Kevin Singewald & Matthew J. Lawless & Joel Caporoso & Nicole Brandon & Jonathan A. Coleman & Sunil Saxena & Erik Lindahl & Yan Xu &, 2022. "Structures of highly flexible intracellular domain of human α7 nicotinic acetylcholine receptor," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28400-x
    DOI: 10.1038/s41467-022-28400-x
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    References listed on IDEAS

    as
    1. Jianjun Pan & Qiang Chen & Dan Willenbring & Ken Yoshida & Tommy Tillman & Ossama B. Kashlan & Aina Cohen & Xiang-Peng Kong & Yan Xu & Pei Tang, 2012. "Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine," Nature Communications, Nature, vol. 3(1), pages 1-8, January.
    2. Ghérici Hassaine & Cédric Deluz & Luigino Grasso & Romain Wyss & Menno B. Tol & Ruud Hovius & Alexandra Graff & Henning Stahlberg & Takashi Tomizaki & Aline Desmyter & Christophe Moreau & Xiao-Dan Li , 2014. "X-ray structure of the mouse serotonin 5-HT3 receptor," Nature, Nature, vol. 512(7514), pages 276-281, August.
    3. Sandip Basak & Yvonne Gicheru & Amrita Samanta & Sudheer Kumar Molugu & Wei Huang & Maria la de Fuente & Taylor Hughes & Derek J. Taylor & Marvin T. Nieman & Vera Moiseenkova-Bell & Sudha Chakrapani, 2018. "Cryo-EM structure of 5-HT3A receptor in its resting conformation," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    4. Lucie Polovinkin & Ghérici Hassaine & Jonathan Perot & Emmanuelle Neumann & Anders A. Jensen & Solène N. Lefebvre & Pierre-Jean Corringer & Jacques Neyton & Christophe Chipot & Francois Dehez & Guy S, 2018. "Conformational transitions of the serotonin 5-HT3 receptor," Nature, Nature, vol. 563(7730), pages 275-279, November.
    5. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
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