Solution structure of the RNA binding domain in the human muscleblind‐like protein 2 |
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Authors: | Fahu He Weirong Dang Chikage Abe Kengo Tsuda Makoto Inoue Satoru Watanabe Naohiro Kobayashi Takanori Kigawa Takayoshi Matsuda Takashi Yabuki Masaaki Aoki Eiko Seki Takushi Harada Yuri Tomabechi Takaho Terada Mikako Shirouzu Akiko Tanaka Peter Güntert Yutaka Muto Shigeyuki Yokoyama |
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Affiliation: | 1. RIKEN Systems and Structural Biology Center, Yokohama 230‐0045, Japan;2. Fahu He and Weirong Dang contributed equally to this work.;3. Tokyo Institute of Technology, Yokohama 226‐8502, Japan;4. Institute of Biophysical Chemistry and Frankfurt Institute of Advanced Studies, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany;5. Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo 113‐0033, Japan |
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Abstract: | The muscleblind‐like (MBNL) proteins 1, 2, and 3, which contain four CCCH zinc finger motifs (ZF1–4), are involved in the differentiation of muscle inclusion by controlling the splicing patterns of several pre‐mRNAs. Especially, MBNL1 plays a crucial role in myotonic dystrophy. The CCCH zinc finger is a sequence motif found in many RNA binding proteins and is suggested to play an important role in the recognition of RNA molecules. Here, we solved the solution structures of both tandem zinc finger (TZF) motifs, TZF12 (comprising ZF1 and ZF2) and TZF34 (ZF3 and ZF4), in MBNL2 from Homo sapiens. In TZF12 of MBNL2, ZF1 and ZF2 adopt a similar fold, as reported previously for the CCCH‐type zinc fingers in the TIS11d protein. The linker between ZF1 and ZF2 in MBNL2 forms an antiparallel β‐sheet with the N‐terminal extension of ZF1. Furthermore, ZF1 and ZF2 in MBNL2 interact with each other through hydrophobic interactions. Consequently, TZF12 forms a single, compact global fold, where ZF1 and ZF2 are approximately symmetrical about the C2 axis. The structure of the second tandem zinc finger (TZF34) in MBNL2 is similar to that of TZF12. This novel three‐dimensional structure of the TZF domains in MBNL2 provides a basis for functional studies of the CCCH‐type zinc finger motifs in the MBNL protein family. |
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Keywords: | NMR solution structure CCCH‐type zinc finger motif muscleblind‐like (MBNL) myotonic dystrophy (DM) |
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