7RPM

Structures of the Intracellular Domain and Transmembrane Domain of the Human alpha7 Nicotinic Acetylcholine Receptors

Summary for 7RPM

• Entry DOI: 10.2210/pdb7rpm/pdb
• NMR Information: BMRB: 30939
• Descriptor: Neuronal acetylcholine receptor subunit alpha-7 (1 entity in total)
• Functional Keywords: nachrs, intracellular domains, ion channels, cys-loop receptors, intrinsically disordered regions, intrinsically disordered proteins, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 5
• Total formula weight: 149158.89

Authors

Bondarenko, V.,Chen, Q.,Tang, P. (deposition date: 2021-08-03, release date: 2022-01-19, Last modification date: 2024-05-15)

Primary citation

Bondarenko, V.,Wells, M.M.,Chen, Q.,Tillman, T.S.,Singewald, K.,Lawless, M.J.,Caporoso, J.,Brandon, N.,Coleman, J.A.,Saxena, S.,Lindahl, E.,Xu, Y.,Tang, P.
Structures of highly flexible intracellular domain of human alpha 7 nicotinic acetylcholine receptor.
Nat Commun, 13:793-793, 2022

PubMed 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.

PubMed: 35145092
DOI: 10.1038/s41467-022-28400-x

Experimental method

SOLUTION NMR