Structural highlights
Disease[ACHA7_HUMAN] 15q13.3 microdeletion syndrome. Function[ACHA7_HUMAN] After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin. Publication Abstract from PubMedThe 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 alpha7 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 A 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. Structures of highly flexible intracellular domain of human alpha7 nicotinic acetylcholine receptor.,Bondarenko V, Wells MM, Chen Q, Tillman TS, Singewald K, Lawless MJ, Caporoso J, Brandon N, Coleman JA, Saxena S, Lindahl E, Xu Y, Tang P Nat Commun. 2022 Feb 10;13(1):793. doi: 10.1038/s41467-022-28400-x. PMID:35145092[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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