期刊
CELL
卷 152, 期 1-2, 页码 183-195出版社
CELL PRESS
DOI: 10.1016/j.cell.2012.12.025
关键词
-
资金
- NIH National Center for Research Resources
- European Community Network of Excellence RUBICON [LSHC-CT-2005-018683]
- Deutsche Forschungsgemeinschaft [CECAD, FOR885, SFB635, HO2541/1-1, HO2541/4-1]
- Austrian Science Fund [FWF P22570-B09]
- Boehringer Ingelheim
- Austrian Science Fund (FWF) [P 22570] Funding Source: researchfish
- Austrian Science Fund (FWF) [P22570] Funding Source: Austrian Science Fund (FWF)
The UCS (UNC-45/CRO1/She4) chaperones play an evolutionarily conserved role in promoting myosin-dependent processes, including cytokinesis, endocytosis, RNA transport, and muscle development. To investigate the protein machinery orchestrating myosin folding and assembly, we performed a comprehensive analysis of Caenorhabditis elegans UNC-45. Our structural and biochemical data demonstrate that UNC-45 forms linear protein chains that offer multiple binding sites for cooperating chaperones and client proteins. Accordingly, Hsp70 and Hsp90, which bind to the TPR domain of UNC-45, could act in concert and with defined periodicity on captured myosin molecules. In vivo analyses reveal the elongated canyon of the UCS domain as a myosin-binding site and show that multimeric UNC-45 chains support organization of sarcomeric repeats. In fact, expression of transgenes blocking UNC-45 chain formation induces dominant-negative defects in the sarcomere structure and function of wild-type worms. Together, these findings uncover a filament assembly factor that directly couples myosin folding with myofilament formation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据