PDF(Pubmed)
Abstract：
Actin, tropomyosin and troponin, the proteins that comprise the contractile apparatus of the cardiac thin filament, are highly conserved across species. We have used cryo-EM to study the three-dimensional structure of the zebrafish cardiac thin and actin filaments. With 70% of human genes having an obvious zebrafish orthologue, and conservation of 85% of disease-causing genes, zebrafish are a good animal model for the study of human disease. Our structure of the zebrafish thin filament reveals the molecular interactions between the constituent proteins, showing that the fundamental organisation of the complex is the same as that reported in the human reconstituted thin filament. A reconstruction of zebrafish cardiac F-actin demonstrates no deviations from human cardiac actin over an extended length of 14 actin subunits. Modelling zebrafish homology models into our maps enabled us to compare, in detail, the similarity with human models. The structural similarities of troponin-T in particular, a region known to contain a hypertrophic cardiomyopathy \'hotspot\', confirm the suitability of zebrafish to study these disease-causing mutations.
摘要：
肌动蛋白,原肌球蛋白和肌钙蛋白,构成心脏细丝收缩装置的蛋白质，在物种之间高度保守。我们已经使用cryo-EM来研究斑马鱼心脏细和肌动蛋白丝的三维结构。70%的人类基因具有明显的斑马鱼直系同源基因，保守85%的致病基因，斑马鱼是研究人类疾病的良好动物模型。我们的斑马鱼细丝的结构揭示了组成蛋白之间的分子相互作用，表明该复合物的基本组织与人类重组细丝中报道的相同。斑马鱼心脏F-肌动蛋白的重建表明，在14个肌动蛋白亚基的延伸长度上，与人类心脏肌动蛋白没有偏差。将斑马鱼同源模型建模到我们的地图中，使我们能够比较，在细节上,与人体模型的相似性。特别是肌钙蛋白T的结构相似性，已知含有肥厚型心肌病的区域，确认斑马鱼是否适合研究这些致病突变。
