XB-ART-58976
Nat Commun
2022 Feb 10;131:793. doi: 10.1038/s41467-022-28400-x.
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Structures of highly flexible intracellular domain of human α7 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
.
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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.
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???displayArticle.grants??? [+]
T32 GM075770 NIGMS NIH HHS , P30 CA047904 NCI NIH HHS , T32 EB009403 NIBIB NIH HHS , R01 DA046939 NIDA NIH HHS
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