...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Molecular cloning of the cDNA encoding the carboxy-terminal domain of chimpanzee apolipoprotein(a): An Asp57 -> Asn mutation in kringle IV-10 is associated with poor fibrin binding
【24h】

Molecular cloning of the cDNA encoding the carboxy-terminal domain of chimpanzee apolipoprotein(a): An Asp57 -> Asn mutation in kringle IV-10 is associated with poor fibrin binding

机译：编码黑猩猩载脂蛋白羧基端结构域（a）的cDNA的分子克隆：kringle IV-10中的Asp57-> Asn突变与纤维蛋白结合不良有关

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

Insight into the structural features of human lipoprotein(a) [Lp(a)] which underlie its functional implication in fibrinolysis may be gained from comparative studies of apo(a). Indeed, cloning of rhesus monkey apo(a) has shown that a Trp72 --> Arg mutation in the lysine-binding site (LBS) of KIV-10 leads to loss of lysine-binding properties of the rhesus Lp(a) particle. Consequently, comparative studies of apo(a) sequences in different Old World monkey species should further our understanding of the molecular role of Lp(a) in the fibrinolytic process. In contrast to other Old World monkeys, including rhesus monkey, cynomolgus, and baboon, the chimpanzee exhibits an elevated level of Lp(a) and a distinct isoform distribution as compared to humans [Doucet et al. J. Lipid Res. (1994) 35, 263-270]. Clearly then, the chimpanzee is an interesting animal model for study of the structure, function, and potential pathophysiological roles of Lp(a). We have cloned and sequenced the region of chimpanzee apo(a) cDNA spanning KIV-3 to the stop codon. The global organization of this region is similar to that of human apo(a) with the presence of KV, which is absent in rhesus monkey apo(a). Nucleotide sequence comparison indicates a variation of 1.4% between chimpanzee and man and 5.1% between chimpanzee and rhesus monkey. The differences concerned single base changes. An Asp57 --> Asn mutation was detected in KIV-10; this residue is critical to the LBS of KIV-10 in human apo(a). To verify that the Asp57 --> Asn substitution was specific to apo(a), we have also cloned the cDNA-encoding plasminogen, which exhibited an Asp at the corresponding position in kringle IV. Using an in vitro binding assay, we have demonstrated that chimpanzee Lp(a) exhibits poor lysine-specific interaction with both intact and plasmin-degraded fibrin as compared to its human counterpart. We propose that the Asn57 substitution in KIV-10 of chimpanzee apo(a) is responsible for this property. Chimpanzee Lp(a) therefore represents an appropriate particle with which to explore the potential effects of Lp(a) on the fibrinolytic system, such as the inhibition of plasminogen activation or inhibition of t-PA activity. [References: 57]
机译：可以通过对apo（a）的比较研究来了解人脂蛋白（a）[Lp（a）]的结构特征，这些结构特征是其在纤维蛋白溶解中的功能含义。确实，恒河猴apo（a）的克隆表明KIV-10赖氨酸结合位点（LBS）中的Trp72-> Arg突变会导致恒河猴Lp（a）颗粒的赖氨酸结合特性丧失。因此，对不同的旧世界猴种中apo（a）序列的比较研究应进一步使我们了解Lp（a）在纤溶过程中的分子作用。与其他旧世界的猴子（包括恒河猴，食蟹猴和狒狒）相比，黑猩猩的Lp（a）水平升高，并且与人相比具有明显的同工型分布[Doucet等，2003年]。 J.脂质研究。 （1994）35，263-270]。显然，黑猩猩是研究Lp（a）的结构，功能和潜在病理生理作用的有趣动物模型。我们已经克隆和测序了跨越KIV-3到终止密码子的黑猩猩apo（a）cDNA区域。该区域的整体组织类似于人类apo（a）的存在，而恒河猴apo（a）中却不存在KV。核苷酸序列比较表明，黑猩猩与人之间的变异为1.4％，黑猩猩与恒河猴之间的变异为5.1％。差异涉及单一基础变更。在KIV-10中检测到Asp57-> Asn突变;该残基对人apo（a）中KIV-10的LBS至关重要。为了验证Asp57-> Asn取代是对apo（a）特异的，我们还克隆了编码cDNA的纤溶酶原，该蛋白在kringle IV的相应位置显示了Asp。使用体外结合试验，我们已经证明，与人类同伴相比，黑猩猩Lp（a）与完整的和纤溶酶降解的纤维蛋白都表现出不良的赖氨酸特异性相互作用。我们建议黑猩猩apo（a）在KIV-10中的Asn57取代是造成此特性的原因。因此，黑猩猩Lp（a）代表一个合适的颗粒，可用来探索Lp（a）对纤溶系统的潜在影响，例如抑制纤溶酶原激活或抑制t-PA活性。 [参考：57]

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