聚聚胺域是狩猎聚合中的种植的主要驱动因素
Adam Skeens1, Chathuranga Siriwardhana1, Sophia E Massinople1
1The C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia, United States of America.
PloS one
|March 14, 2024
概括
亨廷顿病 (HD) 的播种很容易发生在多重氨酸长度上,并且独立于侧面序列. 脂质膜不增强HTT播种,表明多重氨酸域驱动聚合.
科学领域:
- 神经退行性疾病的神经退行性疾病
- 蛋白质聚合蛋白质的聚合.
- 分子生物学分子生物学
背景情况:
- 亨廷顿病 (HD) 是一种致命的神经退行性疾病.
- 蛋白质聚合,特别是具有扩展的多重质胺 (polyQ) 域的亨廷丁蛋白 (htt),形成粉样纤维.
- Htt聚合受侧面序列和脂质膜相互作用的影响.
研究的目的:
- 研究HTT播种在诱导有毒聚合中的作用.
- 确定多Q长度,侧面序列和脂质膜对HTT播种的影响.
主要方法:
- 使用的C. elegans表达非致病性HTT片段.
- 暴露的C.elegans对预先形成的HTT-exon1纤维来诱导播种.
- 多种多Q长度,侧面序列,并引入模型脂质膜.
主要成果:
- 种植诱导毒性聚合和降低活力以剂量依赖的方式.
- Htt播种发生在各种polyQ长度上,并且独立于侧面序列.
- 脂质囊泡改变了播种效率,这表明聚合主要发生在散装溶液中.
结论:
- 粉样纤维体内的多聚胺域是HTT播种的主要驱动因素.
- 播种可以诱导非致病性HTT形式的有毒聚合.
- 聚合似乎发生在散装溶液中,而不是在膜接口上.
相关概念视频
Amyloid Fibrils
9.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.5K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K


