• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >The Antibody Light-Chain Linker Regulates Domain Orientation and Amyloidogenicity
【24h】

The Antibody Light-Chain Linker Regulates Domain Orientation and Amyloidogenicity

机译：抗体轻链接头调节域取向和淀粉样淀作用性

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 antibody light chain (LC) consists of two domains and is essential for antigen binding in mature immunoglobulins. The two domains are connected by a highly conserved linker that comprises the structurally important Arg108 residue. In antibody light chain (AL) amyloidosis, a severe protein amyloid disease, the LC and its N-terminal variable domain (V-L) convert to fibrils deposited in the tissues causing organ failure. Understanding the factors shaping the architecture of the LC is important for basic science, biotechnology and for deciphering the principles that lead to fibril formation. In this study, we examined the structure and properties of LC variants with a mutated or extended linker. We show that under destabilizing conditions, the linker modulates the amyloidogenicity of the LC. The fibril formation propensity of LC linker variants and their susceptibility to proteolysis directly correlate implying an interplay between the two LC domains. Using NMR and residual dipolar coupling-based simulations, we found that the linker residue Arg108 is a key factor regulating the relative orientation of the VL and CL domains, keeping them in a bent and dense, but still flexible conformation. Thus, inter-domain contacts and the relative orientation of VL and CL to each other are of major importance for maintaining the structural integrity of the full-length LC. (C) 2018 Elsevier Ltd. All rights reserved.
机译：抗体轻链（LC）由两个结构域组成，对于成熟免疫球蛋白中的抗原结合是必不可少的。两个结构域通过高度保守的接头连接，该高度保守的接头包括结构上重要的ARG108残基。在抗体轻链（Al）淀粉样蛋白腺苷病中，严重的蛋白质淀粉样疾病，LC及其N-末端可变结构域（V-1）转化为沉积在组织中的原纤维引起器官衰竭。了解塑造LC架构的因素对于基础科学，生物技术和解密导致原纤维形成的原理很重要。在这项研究中，我们检查了LC变体的结构和性质，突变或延伸的连接器。我们表明，在不稳定的条件下，接头调节LC的淀粉样淀。 LC接头变体的原纤维形成倾向及其对蛋白质分解的敏感性直接相关意味着两个LC结构域之间的相互作用。使用NMR和基于偶极耦合的模拟，我们发现接头残留物ARG108是调节VL和CL结构域的相对取向的关键因素，使它们保持弯曲和致密，但仍然是柔性的构象。因此，域间触点和彼此的相对取向对于保持全长LC的结构完整性的主要重要性是主要重要性。 （c）2018年elestvier有限公司保留所有权利。

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