Pokrzywa Wojciech, Hoppe Thorsten
Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD); University of Cologne; Cologne, Germany.
Worm. 2013 Jul 1;2(3):e25644. doi: 10.4161/worm.25644. Epub 2013 Jul 17.
The activity and assembly of various myosin subtypes is coordinated by conserved UCS (UNC-45/CRO1/She4p) domain proteins. One founding member of the UCS family is the Caenorhabditis elegans UNC-45 protein important for the organization of striated muscle filaments. Our recent structural and biochemical results demonstrated that UNC-45 forms a protein chain with defined periodicity of myosin interaction domains. Intriguingly, the UNC-45 chain serves as docking platform for myosin molecules, which promotes ordered spacing and incorporation of myosin into contractile muscle sarcomeres. The physiological relevance of this observation was demonstrated in C. elegans by transgenic expression of UNC-45 chain formation mutants, which provokes defects in muscle structure and size. Collaborating with the molecular chaperones, Hsp70 and Hsp90, chain formation of UNC-45 links myosin folding with myofilament assembly. Here, we discuss our recent findings on the dynamic regulation of UNC-45 structure and stability in the context of muscle regeneration mechanisms that are affected in myopathic diseases and during aging.
各种肌球蛋白亚型的活性和组装由保守的UCS（UNC-45/CRO1/She4p）结构域蛋白协调。UCS家族的一个创始成员是秀丽隐杆线虫UNC-45蛋白，它对横纹肌细丝的组织很重要。我们最近的结构和生化结果表明，UNC-45形成了一条具有肌球蛋白相互作用结构域特定周期性的蛋白质链。有趣的是，UNC-45链作为肌球蛋白分子的对接平台，促进肌球蛋白有序排列并将其纳入收缩性肌节。通过UNC-45链形成突变体的转基因表达在秀丽隐杆线虫中证明了这一观察结果的生理相关性，该突变体引发了肌肉结构和大小的缺陷。与分子伴侣Hsp70和Hsp90合作，UNC-45的链形成将肌球蛋白折叠与肌丝组装联系起来。在这里，我们讨论了我们最近关于在肌病和衰老过程中受影响的肌肉再生机制背景下UNC-45结构和稳定性动态调节的发现。
