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


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.

SUBMITTER: Bondarenko V 

PROVIDER: S-EPMC8831596 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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

Bondarenko Vasyl V   Wells Marta M MM   Chen Qiang Q   Tillman Tommy S TS   Singewald Kevin K   Lawless Matthew J MJ   Caporoso Joel J   Brandon Nicole N   Coleman Jonathan A JA   Saxena Sunil S   Lindahl Erik E   Xu Yan Y   Tang Pei P  

Nature communications 20220210 1


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 l  ...[more]

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