...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Role of the Extracellular Loop in the Folding of a CFTR Transmembrane Helical Hairpin
【24h】

Role of the Extracellular Loop in the Folding of a CFTR Transmembrane Helical Hairpin

机译：细胞外环在CFTR跨膜螺旋发夹折叠中的作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The folding of membrane-spanning domains into their native functional forms depends on interactions between transmembrane(TM)helices joined by covalent loops.However,the importance of these covalent linker regions in mediating the strength of helix-helix associations has not been systematically addressed.Here we examine the potential structural impact of cystic fibrosis-phenotypic mutations in the extracellular loop 2(ECL2)on interactions between the TM3 and TM4 helices of the cystic fibrosis transmembrane conductance regulator(CFTR)in constructs containing CFTR residues 194- 241.When the effects of replacements in ECL2(including the CF-phenotypic mutants E217G and Q220R)were evaluated in a library of wild-type and mutant TM3-ECL2-TM4 hairpin constructs,we found that SDS-PAGE gel migration rates differed over a range of nearly 40% +/- the wild-type position and that decreased migration rates correlate with increasing hairpin alpha-helical content as measured by circular dichroism spectra in sodium dodecyl sulfate micelles.The decreased mobility of TM3/4 constructs by introduction of non-native residues is interpreted in terms of an elongation or "opening" of the helical hairpin and concomitant destabilization of membrane-based helix-helix interactions.Our results support a role for short loop regions in dictating the stability of membrane protein folds and highlight the interplay between membrane-embedded helix-helix interactions and loop conformation in influencing the structure of membrane proteins.
机译：跨膜结构域折叠成其天然功能形式取决于通过共价环连接的跨膜TM螺旋之间的相互作用。然而，这些共价接头区域在介导螺旋-螺旋缔合强度中的重要性尚未得到系统地解决。在这里，我们研究了在含有CFTR残基194-241的构建物中，胞外环2（ECL2）中的囊性纤维化-表型突变对囊性纤维化跨膜电导调节剂（CFTR）的TM3和TM4螺旋之间相互作用的潜在结构影响。在野生型和突变型TM3-ECL2-TM4发夹结构文库中评估了ECL2（包括CF表型突变体E217G和Q220R）替代物的作用，我们发现SDS-PAGE凝胶迁移速率在近乎一个范围内变化40％+/-的野生型位置和降低的迁移率与通过圆二色性斑点测量的发夹α-螺旋含量增加相关通过引入非天然残基来降低TM3 / 4构建体的迁移率，这是根据螺旋发夹的延长或“打开”以及基于膜的螺旋-螺旋相互作用的随之而来的不稳定来解释的。结果支持短环区域在决定膜蛋白折叠稳定性方面的作用，并突出了膜嵌入的螺旋-螺旋相互作用与环构象之间的相互作用对膜蛋白结构的影响。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号