...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Structural alterations of lamin A protein in dilated cardiomyopathy
【24h】

Structural alterations of lamin A protein in dilated cardiomyopathy

机译：扩张型心肌病中Lamin A蛋白的结构改变

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

Lamin A protein, encoded by the LMNA gene, belongs to the type V intermediate filament protein family and is a major nuclear protein component of higher metazoan organisms, including humans. Lamin A along with B-type lamins impart structural rigidity to the nucleus by forming a lamina that is closely apposed to the inner nuclear membrane and is also present as a filamentous network in the interior of the nucleus. A vast number of mutations that lead to a diverse array of at least 11 diseases in humans, collectively termed laminopathies, are being gradually uncovered in the LMNA gene. Dilated cardiomyopathy (DCM) is one such laminopathy in which ventricular dilation leads to an increase in systolic and diastolic volumes, resulting in cardiac arrhythmia and ultimately myocardial infarction. The point mutations in lamin A protein span the entire length of the protein, with a slight preponderance in the central α-helical coiled-coil forming domain. In this work, we have focused on three such important mutations that had been previously observed in DCM-afflicted patients producing severe symptoms. This is the first report to show that these mutations entail significant alterations in the secondary and tertiary structure of the protein, hence perturbing the intrinsic self-association behavior of lamin A protein. Comparison of the enthalpy changes accompanying the deoligomerization process for the wild type and the mutants suggests a difference in the energetics of their self-association. This is further corroborated by the formation of the aggregates of different size and distribution formed inside the nuclei of transfected cells.
机译：由LMNA基因编码的Lamin A蛋白属于V型中间丝蛋白家族，是包括人类在内的高级后生生物的主要核蛋白成分。核纤层蛋白A和B型核纤层蛋白通过形成紧密贴合内核膜的核纤层而赋予核结构刚性，该核纤层也以丝状网络的形式存在于核内。 LMNA基因中逐渐发现了导致人类至少11种疾病的多种突变，这些突变统称为拉米诺病。扩张型心肌病（DCM）是其中一种这样的椎板疾病，其中心室扩张导致收缩和舒张容量增加，从而导致心律不齐，最终导致心肌梗塞。核纤层蛋白A蛋白质中的点突变跨越了蛋白质的整个长度，在中央α-螺旋卷曲螺旋形成域中略占优势。在这项工作中，我们集中研究了以前在DCM严重症状患者中观察到的三个重要突变。这是第一个显示这些突变导致蛋白质二级和三级结构发生重大变化的报告，从而扰乱了层粘蛋白A蛋白的固有自缔合行为。比较野生型和突变型伴随寡聚化过程伴随的焓变，表明它们的自缔合能量不同。通过在转染细胞核内形成不同大小和分布的聚集体进一步证实了这一点。

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