• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Galectin-3 interactions with glycosphingolipids.
【24h】

Galectin-3 interactions with glycosphingolipids.

机译：Galectin-3与糖鞘脂的相互作用。

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

Galectins have essential roles in pathological states including cancer, inflammation, angiogenesis and microbial infections. Endogenous receptors include members of the lacto- and neolacto-series glycosphingolipids present on mammalian cells and contain the tetrasaccharides lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) that form their core structural components and also ganglio-series glycosphingolipids. We present crystallographic structures of the carbohydrate recognition domain of human galectin-3, both wild type and a mutant (K176L) that influenced ligand affinity, in complex with LNT, LNnT and acetamido ganglioside a-GM3 (α2,3-sialyllactose). Key structural features revealed include galectin-3's demonstration of a binding mode towards gangliosides distinct from that to the lactoeolacto-glycosphingolipids, with its capacity for recognising the core β-galactoside region being challenged when the core oligosaccharide epitope of ganglio-series glycosphingolipids (GM3) is embedded within particular higher-molecular-weight glycans. The lacto- and neolacto- glycosphingolipids revealed different orientations of their terminal galactose in the galectin-3-bound LNT and LNnT structures that has significant ramifications for the capacity of galectin-3 to interact with higher-order lactoeolacto-series glycosphingolipids such as ABH blood group antigens and the HNK-1 antigen that is common on leukocytes. LNnT also presents an important model for poly-N-acetyllactosamine-containing glycans and provides insight into galectin-3's accommodation of extended oligosaccharides such as the poly-N-acetyllactosamine-modified N- and O-glycans that, via galectin-3 interaction, facilitate progression of lung and bladder cancers, respectively. These findings provide the first atomic detail of galectin-3's interactions with the core structures of mammalian glycosphingolipids, providing information important in understanding the capacity of galectin-3 to engage with receptors identified as facilitators of major disease.
机译：半乳凝素在包括癌症，炎症，血管生成和微生物感染在内的病理状态中具有重要作用。内源性受体包括存在于哺乳动物细胞上的乳酸和新乳酸系列糖鞘脂的成员，并含有形成其核心结构成分的四糖乳糖-N-四糖（LNT）和乳酸-N-新四糖（LNnT），以及神经节系列糖鞘脂。我们目前与野生型和影响配体亲和力的突变体（K176L）的人类galectin-3的碳水化合物识别域的晶体结构，与LNT，LNnT和乙酰胺神经节苷脂a-GM3（α2,3-唾液乳糖）形成复合体。揭示的关键结构特征包括galectin-3证明了与神经节苷脂的结合模式不同于与乳酸/神经鞘糖脂脂的结合模式，当神经节系列糖鞘脂的核心寡糖表位（ GM3）嵌入特定的高分子量聚糖中。乳和新乳糖鞘糖脂在结合半乳凝素3的LNT和LNnT结构中显示出其末端半乳糖的不同取向，这对半乳凝素3与更高级别的乳/神经系统糖鞘脂相互作用的能力产生了明显影响。 ABH血型抗原和白细胞常见的HNK-1抗原。 LNnT还为含聚N-乙酰基乳糖胺的聚糖提供了一个重要的模型，并深入了解了Galectin-3对扩展寡糖（如经N-galectin-3相互作用的聚N-乙酰基乳糖胺修饰的N-和O-聚糖）的调节，分别促进肺癌和膀胱癌的发展。这些发现提供了galectin-3与哺乳动物糖鞘脂的核心结构相互作用的第一个原子细节，为了解galectin-3与被认为是主要疾病促进因子的受体结合的能力提供了重要信息。

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