2RQA

Solution structure of LGP2 CTD

Summary for 2RQA

• Entry DOI: 10.2210/pdb2rqa/pdb
• Descriptor: ATP-dependent RNA helicase DHX58, ZINC ION (2 entities in total)
• Functional Keywords: rna binding protein, atp-binding, coiled coil, cytoplasm, helicase, hydrolase, immune response, innate immunity, nucleotide-binding, polymorphism, rna-binding
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q96C10
• Total number of polymer chains: 1
• Total formula weight: 15618.42

Authors

Takahasi, K.,Kumeta, H.,Tsuduki, N.,Narita, R.,Shigemoto, T.,Hirai, R.,Yoneyama, M.,Horiuchi, M.,Ogura, K.,Fujita, T.,Fuyuhiko, I. (deposition date: 2009-03-17, release date: 2009-05-05, Last modification date: 2024-11-20)

Primary citation

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., 284:17465-17474, 2009

PubMed 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.

PubMed: 19380577
DOI: 10.1074/jbc.M109.007179

Experimental method

SOLUTION NMR