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タイトル: | Structural Insight into the Recognition of r(UAG) by Musashi-1 RBD2, and Construction of a Model of Musashi-1 RBD1-2 Bound to the Minimum Target RNA |
著者: | Iwaoka, Ryo Nagata, Takashi https://orcid.org/0000-0002-3733-2709 (unconfirmed) Tsuda, Kengo Imai, Takao Okano, Hideyuki Kobayashi, Naohiro Katahira, Masato https://orcid.org/0000-0003-0336-7660 (unconfirmed) |
著者名の別形: | 岩岡, 諒 永田, 崇 片平, 正人 |
キーワード: | RNA-binding protein Msi1 solution structure determination protein-RNA complex |
発行日: | 19-Jul-2017 |
出版者: | MDPI AG |
誌名: | Molecules |
巻: | 22 |
号: | 7 |
論文番号: | 1207 |
抄録: | Musashi-1 (Msi1) controls the maintenance of stem cells and tumorigenesis through binding to its target mRNAs and subsequent translational regulation. Msi1 has two RNA-binding domains (RBDs), RBD1 and RBD2, which recognize r(GUAG) and r(UAG), respectively. These minimal recognition sequences are connected by variable linkers in the Msi1 target mRNAs, however, the molecular mechanism by which Msi1 recognizes its targets is not yet understood. We previously determined the solution structure of the Msi1 RBD1:r(GUAGU) complex. Here, we determined the first structure of the RBD2:r(GUAGU) complex. The structure revealed that the central trinucleotide, r(UAG), is specifically recognized by the intermolecular hydrogen-bonding and aromatic stacking interactions. Importantly, the C-terminal region, which is disordered in the free form, took a certain conformation, resembling a helix. The observation of chemical shift perturbation and intermolecular NOEs, together with increases in the heteronuclear steady-state {1H}-15N NOE values on complex formation, indicated the involvement of the C-terminal region in RNA binding. On the basis of the two complex structures, we built a structural model of consecutive RBDs with r(UAGGUAG) containing both minimal recognition sequences, which resulted in no steric hindrance. The model suggests recognition of variable lengths (n) of the linker up to n = 50 may be possible. |
著作権等: | © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0). |
URI: | http://hdl.handle.net/2433/233073 |
DOI(出版社版): | 10.3390/molecules22071207 |
PubMed ID: | 28753936 |
出現コレクション: | 学術雑誌掲載論文等 |
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