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

• DOI: 10.1038/s41467-022-28400-x
• Publication Date: 2022-02-10T11:03:54Z
• Authors: 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; Pei Tang
• Keywords: Helix (gastropod)

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