2QFD

Crystal structure of the regulatory domain of human RIG-I with bound Hg

Summary for 2QFD

• Entry DOI: 10.2210/pdb2qfd/pdb
• Related: 2QFB
• Descriptor: Probable ATP-dependent RNA helicase DDX58, MERCURY (II) ION (3 entities in total)
• Functional Keywords: zinc finger, alternative splicing, antiviral defense, atp-binding, helicase, hydrolase, immune response, innate immunity, interferon induction, nucleotide-binding, polymorphism, rna-binding, ubl conjugation
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O95786
• Total number of polymer chains: 10
• Total formula weight: 170540.88

Authors

Cui, S.,Lammens, A.,Lammens, K.,Hopfner, K.P. (deposition date: 2007-06-27, release date: 2008-02-12, Last modification date: 2024-10-30)

Primary citation

Cui, S.,Eisenacher, K.,Kirchhofer, A.,Brzozka, K.,Lammens, A.,Lammens, K.,Fujita, T.,Conzelmann, K.K.,Krug, A.,Hopfner, K.P.
The C-Terminal Regulatory Domain Is the RNA 5'-Triphosphate Sensor of RIG-I.
Mol.Cell, 29:169-179, 2008

PubMed Abstract: The ATPase RIG-I senses viral RNAs that contain 5'-triphosphates in the cytoplasm. It initiates a signaling cascade that activates innate immune response by interferon and cytokine production, providing essential antiviral protection for the host. The mode of RNA 5'-triphosphate sensing by RIG-I remains elusive. We show that the C-terminal regulatory domain RD of RIG-I binds viral RNA in a 5'-triphosphate-dependent manner and activates the RIG-I ATPase by RNA-dependent dimerization. The crystal structure of RD reveals a zinc-binding domain that is structurally related to GDP/GTP exchange factors of Rab-like GTPases. The zinc coordination site is essential for RIG-I signaling and is also conserved in MDA5 and LGP2, suggesting related RD domains in all three enzymes. Structure-guided mutagenesis identifies a positively charged groove as likely 5'-triphosphate-binding site of RIG-I. This groove is distinct in MDA5 and LGP2, raising the possibility that RD confers ligand specificity.

PubMed: 18243112
DOI: 10.1016/j.molcel.2007.10.032

Experimental method

X-RAY DIFFRACTION (2.7 Å)