• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >Differences in solution dynamics between lens β-crystallin homodimers and heterodimers probed by hydrogen-deuterium exchange and deamidation
【2h】

Differences in solution dynamics between lens β-crystallin homodimers and heterodimers probed by hydrogen-deuterium exchange and deamidation

机译：氢-氘交换和脱酰胺法检测晶状体β-晶体蛋白同二聚体和异二聚体的溶液动力学差异

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

- Background: Lens transparency is due to the ordered arrangement of the major structural proteins, called crystallins. βB2 crystallin in the lens of the eye readily forms dimers with other β-crystallin subunits, but the resulting heterodimer structures are not known and were investigated in this study.\ud- Methods: Structures of βA3 and βB2 crystallin homodimers and the βA3/βB2 crystallin heterodimers were probed by measuring changes in solvent accessibility using hydrogen–deuterium exchange with mass spectrometry. We further mimicked deamidation in βB2 and probed the effect on the βA3/βB2 heterodimer. Results were confirmed with chemical crosslinking and NMR.\ud- Results: Both βA3 and βB2 had significantly decreased deuterium levels in the heterodimer compared to their respective homodimers, suggesting that they had less solvent accessibility and were more compact in the heterodimer. The compact structure of βB2 was supported by the identification of chemical crosslinks between lysines in βB2 within the heterodimer that were inconsistent with βB2's extended homodimeric structure. The compact structure of βA3 was supported by an overall decrease in mobility of βA3 in the heterodimer detected by NMR.\ud\udIn βB2, peptides 70–84 and 121–134 were exposed in the homodimer, but buried in the heterodimer with ≥ 50% decreases in deuterium levels. Homologous peptides in βA3, 97–109 and 134–149, had 25–50% decreases in deuterium levels in the heterodimer. These peptides are probable sites of interaction between βB2 and βA3 and are located at the predicted interface between subunits with bent linkers. Deamidation at Q184 in βB2 at this predicted interface led to a less compact βB2 in the heterodimer.\ud\udThe more compact structure of the βA3/βB2 heterodimer was also more heat stable than either of the homodimers.\ud- Conclusions: The major structural proteins in the lens, the β-crystallins, are not static, but dynamic in solution, with differences in accessibility between the homo-and hetero-dimers. This structural flexibility, particularly of βB2, may facilitate formation of different size higher-ordered structures found in the transparent lens.\ud- General significance: Understanding complex hetero-oligomer interactions between β-crystallins in normal lens and how these interactions change during aging is fundamental to understanding the cause of cataracts.
机译：-背景：晶状体透明性是由于主要结构蛋白（称为晶状蛋白）的有序排列所致。晶状体中的βB2晶状体蛋白容易与其他β-晶状体蛋白亚基形成二聚体，但尚不知道所形成的异二聚体结构，并在本研究中进行了研究。\ ud-方法：βA3和βB2晶状体同质二聚体以及βA3/βB2的结构通过使用氢-氘交换和质谱法测量溶剂可及性的变化来探究晶体蛋白异二聚体。我们进一步模拟了βB2中的脱酰胺作用，并探讨了其对βA3/βB2异二聚体的影响。结果通过化学交联和NMR证实。\ ud-结果：与它们各自的同型二聚体相比，βA3和βB2的异二聚体中的氘含量均显着降低，表明它们的溶剂可及性较低，并且在异二聚体中更为紧密。鉴定异二聚体中βB2中赖氨酸之间的化学交联与βB2的延伸同二聚体结构不一致，从而支持了βB2的紧凑结构。通过核磁共振检测到的异源二聚体中βA3迁移率的总体下降，支持了βA3的紧凑结构。\ ud \ ud在βB2中，肽70–84和121–134暴露于同二聚体中，但被埋在≥50的异二聚体中％的氘水平降低。 βA3的同源肽，97–109和134–149，异二聚体中的氘水平降低了25–50％。这些肽可能是βB2和βA3之间相互作用的位点，位于带有弯曲接头的亚基之间的预测界面上。在该预测界面处，βB2在Q184处的脱酰胺作用导致异二聚体中的βB2致密性降低。\ ud \udβA3/βB2异质二聚体的更致密结构也比同一个二聚体更热稳定。\ ud-结论：主要晶状体中的结构蛋白，即β-晶状蛋白，不是静态的，而是在溶液中动态的，同二聚体和异二聚体之间的可及性有所不同。这种结构的灵活性，尤其是βB2的柔性，可能有助于形成透明晶状体中不同大小的高阶结构。\ ud-一般意义：理解正常晶状体中β-晶状蛋白之间复杂的异低聚物相互作用以及这些相互作用在老化过程中如何变化是了解白内障病因的基础。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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