...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Crystal structure of human α-tocopherol transfer protein bound to its ligand: Implications for ataxia with vitamin E deficiency
【24h】

Crystal structure of human α-tocopherol transfer protein bound to its ligand: Implications for ataxia with vitamin E deficiency

机译：人α-生育酚转移蛋白与其配体结合的晶体结构：对维生素E缺乏共济失调的影响

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

Human a-tocopherol (α-T) transfer protein (ATTP) plays a central role in vitamin E homeostasis, preventing degradation of α-T by routing this lipophilic molecule for secretion by hepatocytes. Mutations in the gene encoding ATTP have been shown to cause a severe deficiency in α-T, which results in a progressive neurode-generative spinocerebellar ataxia, known as ataxia with vitamin E deficiency (AVED). We have determined the high-resolution crystal structure of human ATTP with (2R,4'R,8'R)-α-T in the binding pocket. Surprisingly, the ligand is sequestered deep in the hydro-phobic core of the protein, implicating a large structural rearrangement for the entry and release of α-T. A comparison to the structure of a related protein, Sec14p, crystallized without a bona fide ligand, shows a possibly relevant open conformation for this family of proteins. Furthermore, of the known mutations that cause AVED, one mutation, L183P, is located directly in the binding pocket. Finally, three mutations associated with AVED involve arginine residues that are grouped together on the surface of ATTP. We propose that this positively charged surface may serve to orient an interacting protein, which might function to regulate the release of α-T through an induced change in conformation of ATTP.
机译：人α-生育酚（α-T）转移蛋白（ATTP）在维生素E体内平衡中起着核心作用，通过将这种亲脂性分子传递给肝细胞分泌来防止α-T降解。业已证明，编码ATTP的基因突变会导致α-T严重缺乏，从而导致进行性神经退行性脊髓小脑性共济失调，称为维生素E缺乏共济失调（AVED）。我们已经确定了在结合袋中具有（2R，4'R，8'R）-α-T的人类ATTP的高分辨率晶体结构。出人意料的是，该配体被螯合在该蛋白质的疏水核心的深处，暗示了α-T进入和释放的大结构重排。与没有真正配体的情况下结晶的相关蛋白质Sec14p的结构比较表明，该蛋白质家族可能具有相关的开放构象。此外，在引起AVED的已知突变中，一个突变L183P直接位于结合袋中。最后，与AVED相关的三个突变涉及精氨酸残基，这些残基在ATTP表面组合在一起。我们建议，该带正电荷的表面可能用于定向相互作用的蛋白质，该蛋白质可能通过诱导ATTP构象变化来调节α-T的释放。

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