...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >A Complex Dance: The Importance of Glycosaminoglycans and Zinc in the Aggregation of Human Prolactin
【24h】

A Complex Dance: The Importance of Glycosaminoglycans and Zinc in the Aggregation of Human Prolactin

机译：复杂的舞蹈：糖胺聚糖和锌在人类催乳素聚集中的重要性

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 zinc binding hormone pituitary human prolactin (hPRL) is stored in secretory granules of specialized cells in an aggregated form. Glycosaminoglycans (GAGs) are anionic polysaccharides commonly associated with secretory granules, indicating their involvement in granule formation. Here we, for the first time, study the impact of GAGs in combination with Zn2+ on the reversible hPRL aggregation across the pH range of 7.4-5.5. Zn2+ alone causes hPRL aggregation at pH 7.4, while aggregation between pH 7.4 and 5.5 requires both Zn2+ and GAGs. GAGs alone cause hPRL aggregation below pH 5.5. Comprehensive thermal stability investigations show that hPRL is particularly destabilized toward thermal denaturation at pH 5.5 and that GAGs increasingly destabilize hPRL at decreasing pH values. We propose that Zn2+ causes hPRL aggregation through low-affinity Zn2+ binding sites on hPRL with GAGs facilitating Zn2+ binding by neutralizing repulsive positive charges of hPRL in the acidic environments of the TGN and mature secretory granules. In a manner independent of the aggregation-causing agent(s), the different hPRL aggregates show very similar secondary structure and amorphous morphology. We speculate that this may be a recognizable sorting signal in the formation of hPRL granular vesicles.
机译：锌结合激素垂体人类催乳素（hPRL）以聚集形式存储在专门细胞的分泌颗粒中。糖胺聚糖（GAG）是通常与分泌颗粒相关的阴离子多糖，表明它们参与颗粒形成。在这里，我们首次研究了GAG与Zn2 +结合在7.4-5.5的pH范围内对可逆hPRL聚集的影响。单独的Zn2 +会在pH 7.4时引起hPRL聚集，而在pH 7.4和5.5之间的聚集则需要Zn2 +和GAG。单独的GAG会导致hPRL聚集在pH 5.5以下。全面的热稳定性研究表明，hPRL在pH 5.5下对热变性特别不稳定，并且GAG在pH值降低时逐渐使hPRL不稳定。我们提出，Zn2 +通过hPRL上的低亲和力Zn2 +结合位点引起hPRL聚集，GAG通过中和TGN和成熟分泌颗粒的酸性环境中的hPRL排斥性正电荷促进Zn2 +结合。以独立于导致聚集剂的方式，不同的hPRL聚集体显示出非常相似的二级结构和无定形形态。我们推测这可能是hPRL颗粒囊泡形成中可识别的分类信号。

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