Structures of highly flexible intracellular domain of human α7 nicotinic acetylcholine receptor.
Structures of highly flexible intracellular domain of human α7 nicotinic acetylcholine receptor.
复制标题
人α7烟碱型乙酰胆碱受体高柔性胞内结构域的结构。
DOI：
10.1038/s41467-022-28400-x
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发表时间：
2022-02-10
影响因子：
16.6
通讯作者：
Tang P
中科院分区：
文献类型：
--
作者：
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
Cys环受体的胞内结构域（ICD）介导多种功能。迄今为止，由于其动态性质带来的挑战，没有完整的ICD结构。在这里，结合核磁共振（NMR）和电子自旋共振实验与罗塞塔计算，我们确定全长ICD结构的人α7烟碱乙酰胆碱受体在静息状态。我们发现，约57%的ICD残基是在高度灵活的区域，主要是在一个大的环（环L）与最移动的段跨越约50埃从中央通道轴。环L锚定在MA螺旋上，实际上形成两个较小的环，从而增加其稳定性。先前已知的细胞质结合，调节和信号传导的基序被发现在螺旋和无序的柔性区域中，支持ICD构象可塑性在协调广泛的生物过程中的重要作用。Cys环受体的胞内结构域（ICD）介导它们的许多功能，但迄今为止没有Cys环受体ICD的完整结构。在这里，作者结合联合收割机核磁共振和ESR光谱，以确定全长ICD结构的人α7烟碱乙酰胆碱受体（α 7 nAChR）。
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. The intracellular domain (ICD) of Cys-loop receptors mediates many of their functions, but no complete structure of a Cys-loop receptor ICD is available to date. Here, the authors combine NMR and ESR spectroscopy to determine the full-length ICD structures of the human α7 nicotinic acetylcholine receptor (α7nAChR).
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
DOI：
10.1523/jneurosci.6344-09.2010
发表时间：
2010-07-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Alexander JK;Sagher D;Krivoshein AV;Criado M;Jefford G;Green WN
通讯作者：
Green WN
影响因子：
2.7
作者：
Baxter, NJ;Williamson, MP
通讯作者：
Williamson, MP
影响因子：
2.9
作者：
FARROW, NA;MUHANDIRAM, R;KAY, LE
通讯作者：
KAY, LE