期刊
CHEMBIOCHEM
卷 13, 期 1, 页码 112-119出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201100487
关键词
fluorescence quenching; helix destabilization; myotonic dystrophy; protein-RNA complexes; RNA
资金
- NIAMS NIH HHS [R01 AR058361, R01 AR058361-01, R01AR058361S] Funding Source: Medline
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [0843728] Funding Source: National Science Foundation
Muscleblind-like proteins (MBNL) are RNA-binding proteins that bind to the poly(CUG) and poly(CCUG) sequences that are the causative agents of myotonic dystrophy. It has been suggested that as a result of binding to the repeating RNA sequences, MBNL1 is abnormally expressed and translocated, which leads to many of the misregulated events in myotonic dystrophy. In this work, steady-state fluorescence quenching experiments suggest that MBNL1 alters the structure of helical RNA targets upon binding, which may explain the selectivity of MBNL1 for less structured RNA sites. The removal of one pair of zinc fingers greatly impairs the binding affinity of MBNL1, which indicates that the two pairs of zinc fingers might possibly interact with RNA targets cooperatively. Alanine scanning mutagenesis results suggest that the binding energy may be distributed across the protein. Overall, the results presented here suggest that small molecules that stabilize the helical structure of poly(CUG) and poly(CCUG) RNAs will inhibit the formation of complexes with MBNL1.
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