Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility.
Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility.
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DOI：
10.1038/s41467-022-34017-x
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发表时间：
2022-10-20
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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由普雷斯廷驱动的外毛细胞电活动性对于哺乳动物耳蜗放大是必不可少的。在这里，我们报告的cryo-EM结构的热稳定的普雷斯廷（PresTS），与氯化物，硫酸盐，或水杨酸盐在3.52-3.63毫米分辨率。中心带正电荷的空腔允许各种阴离子物质的灵活结合，这可能是由于不同阴离子对非线性电容（NLC）的已知不同调制。这些PresTS结构与最近的普雷斯廷结构的比较表明，核心和门域之间的刚体运动，并提供水杨酸盐抑制普雷斯廷的机制的见解。二聚体界面处的突变严重减少NLC，表明门结构域的稳定促进核心结构域移动，从而有助于NLC的表达。这些发现推进了我们对哺乳动物耳蜗放大的分子机制的理解。由普雷斯廷驱动的外毛细胞电活动对于哺乳动物耳蜗放大是必不可少的。在这里，作者报告了在各种阴离子的存在下，热稳定的普雷斯廷的冷冻电镜结构，提供了深入了解哺乳动物耳蜗放大的机制。
Outer hair cell elecromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, we report the cryo-EM structures of thermostabilized prestin (PresTS), complexed with chloride, sulfate, or salicylate at 3.52-3.63 Å resolutions. The central positively-charged cavity allows flexible binding of various anion species, which likely accounts for the known distinct modulations of nonlinear capacitance (NLC) by different anions. Comparisons of these PresTS structures with recent prestin structures suggest rigid-body movement between the core and gate domains, and provide mechanistic insights into prestin inhibition by salicylate. Mutations at the dimeric interface severely diminished NLC, suggesting that stabilization of the gate domain facilitates core domain movement, thereby contributing to the expression of NLC. These findings advance our understanding of the molecular mechanism underlying mammalian cochlear amplification. Outer hair cell electromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, the authors report the cryo-EM structures of thermostabilized prestin in the presence of various anions, providing insight into the mechanisms of mammalian cochlear amplification.
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影响因子：
64.8
作者：
Canul-Tec JC;Assal R;Cirri E;Legrand P;Brier S;Chamot-Rooke J;Reyes N
通讯作者：
Reyes N
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
影响因子：
4.4
作者：
FELLER, SE;ZHANG, YH;BROOKS, BR
通讯作者：
BROOKS, BR
DOI：
10.1107/s2059798318006551
发表时间：
2018-06-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Afonine PV;Poon BK;Read RJ;Sobolev OV;Terwilliger TC;Urzhumtsev A;Adams PD
通讯作者：
Adams PD
影响因子：
16.2
作者：
Dallos, Peter;Wu, Xudong;Zuo, Jian
通讯作者：
Zuo, Jian