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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

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