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  • Bondarenko, VasylUniv Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA. (author)

Structures of highly flexible intracellular domain of human alpha 7 nicotinic acetylcholine receptor

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-02-10
  • Springer Nature,2022
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-309440
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-309440URI
  • https://doi.org/10.1038/s41467-022-28400-xDOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-202744URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20220304
  • 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 alpha 7 nicotinic acetylcholine receptor in a resting state. We show that similar to 57% of the ICD residues are in highly flexible regions, primarily in a large loop (loop L) with the most mobile segment spanning similar to 50 angstrom 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Wells, Marta M.Univ Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA. (author)
  • Chen, QiangUniv Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA. (author)
  • Tillman, Tommy S.Univ Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA.,Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. (author)
  • Singewald, KevinUniv Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. (author)
  • Lawless, Matthew J.Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. (author)
  • Caporoso, JoelUniv Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA. (author)
  • Brandon, NicoleUniv Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA. (author)
  • Coleman, Jonathan A.Univ Pittsburgh, Dept Struct Biol, Pittsburgh, PA 15260 USA. (author)
  • Saxena, SunilUniv Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. (author)
  • Lindahl, Erik,1972-Stockholms universitet,KTH,SeRC - Swedish e-Science Research Centre,Tillämpad fysik,Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Solna, Sweden.,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),KTH Royal Institute of Technology, Sweden(Swepub:su)erlin (author)
  • Xu, YanUniv Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Struct Biol, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Phys & Astron, Pittsburgh, PA 15260 USA. (author)
  • Tang, PeiUniv Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA. (author)
  • Univ Pittsburgh, Dept Anesthesiol & Perioperat Med, Pittsburgh, PA 15260 USA.Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. (creator_code:org_t)

Related titles

  • In:Nature Communications: Springer Nature13:12041-1723

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