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2rqb
From Proteopedia
| 2rqb () | |||||||||
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| Sites: | |||||||||
| Ligands: | |||||||||
| Gene: | IFIH1, MDA5, RH116 (Homo sapiens) | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Solution structure of MDA5 CTD
The RIG-I like receptor (RLR) comprises three homologues: RIG-I (Retionic 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;f-triphosphated single stranded RNA (5;fppp-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;fppp-ssRNA are bound to the basic surface of LGP2 CTD while 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;fppp-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.
Solution structures of cytosolic RNA sensors MDA5 and LGP2 C-terminal domains: Identification of the RNA recognition loop in RIG-I like receptors., Takahasi K, Kumeta H, Tsuduki N, Narita R, Shigemoto T, Hirai R, Yoneyama M, Horiuchi M, Ogura K, Fujita T, Inagaki F, J Biol Chem. 2009 Apr 20. PMID:19380577
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2RQB is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Takahasi K, Kumeta H, Tsuduki N, Narita R, Shigemoto T, Hirai R, Yoneyama M, Horiuchi M, Ogura K, Fujita T, Inagaki F. Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors. J Biol Chem. 2009 Jun 26;284(26):17465-74. Epub 2009 Apr 20. PMID:19380577 doi:10.1074/jbc.M109.007179
Page seeded by OCA on Wed Jul 8 20:03:12 2009
Categories: Homo sapiens | Fujita, T. | Fuyuhiko, I. | Hirai, R. | Horiuchi, M. | Kumeta, H. | Narita, R. | Ogura, K. | Shigemoto, T. | Takahasi, K. | Tsuduki, N. | Yoneyama, M. | Alternative splicing | Antiviral defense | Atp-binding | Cytoplasm | Diabetes mellitus | Helicase | Host-virus interaction | Hydrolase | Immune response | Innate immunity | Nucleotide-binding | Nucleus | Phosphoprotein | Polymorphism | Rna binding protein | Rna-binding
