| Title: | Solution Structures of Cytosolic RNA Sensor MDA5 and LGP2 C-terminal Domains : Identification of the RNA Recognition Loop in RIG-I-LIKE Receptors |
| Authors: | Takahasi, Kiyohiro Browse this author |
| Kumeta, Hiroyuki Browse this author |
| Tsuduki, Natsuko Browse this author |
| Narita, Ryo Browse this author |
| Shigemoto, Taeko Browse this author |
| Hirai, Reiko Browse this author |
| Yoneyama, Mitsutoshi Browse this author |
| Horiuchi, Masataka Browse this author |
| Ogura, Kenji Browse this author |
| Fujita, Takashi Browse this author |
| Inagaki, Fuyuhiko Browse this author |
| Issue Date: | 26-Jun-2009 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 284 |
| Issue: | 26 |
| Start Page: | 17465 |
| End Page: | 17474 |
| Publisher DOI: | 10.1074/jbc.M109.007179 |
| Abstract: | The RIG-I like receptor (RLR) comprises three homologues: RIG-I (retinoic acid-inducible gene I), MDA5(melanoma differentiation-associated gene 5), and LGP2 (laboratory of genetics and physiology 2). Each RLR senses different viral infections by recognizing replicating viral RNA in the cytoplasm. The RLR contains a conserved C-terminal domain (CTD), which is responsible for the binding specificity to the viral RNAs, including double-stranded RNA (dsRNA) and 5'-triphosphated single-stranded RNA (5'ppp-ssRNA). Here, the solution structures of the MDA5 and LGP2 CTD domains were solved by NMR and compared with those of RIG-I CTD. The CTD domains each have a similar fold and a similar basic surface but there is the distinct structural feature of a RNA binding loop; The LGP2 and RIG-I CTD domains have a large basic surface, one bank of which is formed by the RNA binding loop. MDA5 also has a large basic surface that is extensively flat due to open conformation of the RNA binding loop. The NMR chemical shift perturbation study showed that dsRNA and 5'ppp-ssRNA are bound to the basic surface of LGP2 CTD, whereas dsRNA is bound to the basic surface of MDA5 CTD but much more weakly, indicating that the conformation of the RNA binding loop is responsible for the sensitivity to dsRNA and 5'ppp-ssRNA. Mutation study of the basic surface and the RNA binding loop supports the conclusion from the structure studies. Thus, the CTD is responsible for the binding affinity to the viral RNAs. |
| Rights: | © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/38780 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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