• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >The molecular basis for sugar import in malaria parasites
【24h】

The molecular basis for sugar import in malaria parasites

机译：疟原虫中糖进口的分子基础

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

Elucidating the mechanism of sugar import requires a molecular understanding of how transporters couple sugar binding and gating events. Whereas mammalian glucose transporters (GLUTs) are specialists(1), the hexose transporter from the malaria parasite Plasmodium falciparum PfHT1(2,3) has acquired the ability to transport both glucose and fructose sugars as efficiently as the dedicated glucose (GLUT3) and fructose (GLUT5) transporters. Here, to establish the molecular basis of sugar promiscuity in malaria parasites, we determined the crystal structure of PfHT1 in complex with d-glucose at a resolution of 3.6 angstrom. We found that the sugar-binding site in PfHT1 is very similar to those of the distantly related GLUT3 and GLUT5 structures(4,5). Nevertheless, engineered PfHT1 mutations made to match GLUT sugar-binding sites did not shift sugar preferences. The extracellular substrate-gating helix TM7b in PfHT1 was positioned in a fully occluded conformation, providing a unique glimpse into how sugar binding and gating are coupled. We determined that polar contacts between TM7b and TM1 (located about 15 angstrom from d-glucose) are just as critical for transport as the residues that directly coordinate d-glucose, which demonstrates a strong allosteric coupling between sugar binding and gating. We conclude that PfHT1 has achieved substrate promiscuity not by modifying its sugar-binding site, but instead by evolving substrate-gating dynamics.Crystal structure of the Plasmodium falciparum hexose transporter PfHT1 reveals the molecular basis of its ability to transport multiple types of sugar as efficiently as the dedicated mammalian glucose and fructose transporters.
机译：阐明糖进口的机制需要对转运蛋白如何结合糖结合和门控事件进行分子理解。哺乳动物葡萄糖转运蛋白（GLUTs）是专家（1），疟疾寄生虫恶性疟原虫PfHT1（2,3）中的己糖转运蛋白具有与专用葡萄糖（GLUT3）和果糖一样有效的转运葡萄糖和果糖的能力。 （GLUT5）转运蛋白。在这里，为了建立疟疾寄生虫中糖滥的分子基础，我们确定了与d-葡萄糖复合的PfHT1的晶体结构，分辨率为3.6埃。我们发现PfHT1中的糖结合位点与远距离相关的GLUT3和GLUT5结构的糖结合位点非常相似（4,5）。尽管如此，为匹配GLUT糖结合位点而设计的工程化PfHT1突变并没有改变糖的偏好。 PfHT1中的细胞外底物门控螺旋TM7b处于完全封闭的构象，从而提供了糖结合和门控耦合的独特视角。我们确定，TM7b和TM1之间的极性接触（距d-葡萄糖约15埃）对于转运至关重要，与直接协调d-葡萄糖的残基一样，这表明糖结合和门控之间存在很强的变构偶联。我们得出的结论是，PfHT1并非通过修饰其糖结合位点来实现底物滥交，而是通过进化底物门控动力学来实现的.Falciparum恶性疟原丝己糖转运蛋白的晶体结构揭示了其有效转运多种类型糖的能力的分子基础。作为哺乳动物专用的葡萄糖和果糖转运蛋白。

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