The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
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囊性纤维化跨膜电导调节器 (CFTR)
DOI：
--
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发表时间：
2011
影响因子：
4.8
通讯作者：
R. Ford
中科院分区：
文献类型：
--
作者：
M. Rosenberg;Liam O'Ryan;G. Hughes;Zhefeng Zhao;Luba A. Aleksandrov;J. Riordan;R. Ford
背景：囊性纤维化是一种cftr基因突变导致氯离子通道丧失的疾病。结果：CFTR跨膜结构域呈外向构型。结论：该图谱显示了可能代表通道门及其调控区的区域。意义：与通道功能变化和疾病相关的残基邻近门。囊性纤维化影响约1/2500活产，并涉及由于缺乏称为囊性纤维化跨膜传导调节因子（CFTR）的膜蛋白通道而导致的跨膜氯离子通量损失。我们用电子晶体学方法研究了CFTR的结构。与其他ATP结合盒转运蛋白的现有结构的数据进行了比较。该蛋白质结晶在面向外的状态，并类似于良好的特点Sav 1866转运。我们在CFTR图中确定了Sav 1866未考虑的区域，这些区域是调控区和通道门的潜在位置。在这个分析中，我们得到了这样一个事实的帮助，即晶胞是由两个不具有晶体学对称性的分子组成的。我们还在拟合的Sav 1866模型中确定了地图中缺失的区域，因此与Sav 1866相比，CFTR中的区域要么是无序的，要么是不同的组织。除N和C末端外，这表明在CFTR中，跨膜螺旋5/11的胞质末端及其相关环可以部分无序（或交替定位）。
Background: Cystic fibrosis is a disease where mutations in the cftr gene lead to loss of a chloride channel. Results: The CFTR transmembrane domains show an outward facing configuration. Conclusion: The map shows regions that probably represent the channel's gate and its regulatory region. Significance: Residues associated with changes in channel function and disease are adjacent to the gate. Cystic fibrosis affects about 1 in 2500 live births and involves loss of transmembrane chloride flux due to a lack of a membrane protein channel termed the cystic fibrosis transmembrane conductance regulator (CFTR). We have studied CFTR structure by electron crystallography. The data were compared with existing structures of other ATP-binding cassette transporters. The protein was crystallized in the outward facing state and resembled the well characterized Sav1866 transporter. We identified regions in the CFTR map, not accounted for by Sav1866, which were potential locations for the regulatory region as well as the channel gate. In this analysis, we were aided by the fact that the unit cell was composed of two molecules not related by crystallographic symmetry. We also identified regions in the fitted Sav1866 model that were missing from the map, hence regions that were either disordered in CFTR or differently organized compared with Sav1866. Apart from the N and C termini, this indicated that in CFTR, the cytoplasmic end of transmembrane helix 5/11 and its associated loop could be partly disordered (or alternatively located).
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通过电子显微镜和金标记研究囊性纤维化跨膜电导调节蛋白内的结构域位置。
DOI：
10.1016/j.bbamem.2010.08.012
发表时间：
2011
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Zhang,Liang;Aleksandrov,LubaA;Riordan,JohnR;Ford,RobertC
通讯作者：
Ford,RobertC
影响因子：
56.9
作者：
J. Riordan;J. Rommens;N. Alon;R. Rozmahel;Z. Grzelczak;J. Zieleński;N. Plavsic;Jia-Ling Chou
通讯作者：
J. Riordan;J. Rommens;N. Alon;R. Rozmahel;Z. Grzelczak;J. Zieleński;N. Plavsic;Jia-Ling Chou
影响因子：
19
作者：
McIntosh, R;Nicastro, D;Mastronarde, D
通讯作者：
Mastronarde, D
囊性纤维化跨膜电导调节蛋白的结构以及与磷酸化和核苷酸结合相关的结构变化。
影响因子：
3
作者：
Zhang,Liang;Aleksandrov,LubaA;Zhao,Zhefeng;Birtley,JamesR;Riordan,JohnR;Ford,RobertC
通讯作者：
Ford,RobertC
影响因子：
16
作者：
Khare, Dheeraj;Oldham, Michael L.;Orelle, Cedric;Davidson, Amy L.;Chen, Jue
通讯作者：
Chen, Jue