2W4R

Crystal structure of the regulatory domain of human LGP2

2W4R の概要

• エントリーDOI: 10.2210/pdb2w4r/pdb
• 分子名称: PROBABLE ATP-DEPENDENT RNA HELICASE DHX58, MERCURY (II) ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: innate immunity, immune response, nucleotide-binding, coiled coil, atp-binding, polymorphism, double-strand rna binding protein, helicase, hydrolase, cytoplasm, rna-binding
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q96C10
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 66137.29

構造登録者

Pippig, D.A.,Hellmuth, J.C.,Cui, S.,Kirchhofer, A.,Lammens, K.,Lammens, A.,Schmidt, A.,Rothenfusser, S.,Hopfner, K.P. (登録日: 2008-12-01, 公開日: 2009-02-24, 最終更新日: 2024-11-20)

主引用文献

Pippig, D.A.,Hellmuth, J.C.,Cui, S.,Kirchhofer, A.,Lammens, K.,Lammens, A.,Schmidt, A.,Rothenfusser, S.,Hopfner, K.P.
The Regulatory Domain of the Rig-I Family ATPase Lgp2 Senses Double-Stranded RNA.
Nucleic Acids Res., 37:2014-, 2009

PubMed Abstract: RIG-I and MDA5 sense cytoplasmic viral RNA and set-off a signal transduction cascade, leading to antiviral innate immune response. The third RIG-I-like receptor, LGP2, differentially regulates RIG-I- and MDA5-dependent RNA sensing in an unknown manner. All three receptors possess a C-terminal regulatory domain (RD), which in the case of RIG-I senses the viral pattern 5'-triphosphate RNA and activates ATP-dependent signaling by RIG-I. Here we report the 2.6 A crystal structure of LGP2 RD along with in vitro and in vivo functional analyses and a homology model of MDA5 RD. Although LGP2 RD is structurally related to RIG-I RD, we find it rather binds double-stranded RNA (dsRNA) and this binding is independent of 5'-triphosphates. We identify conserved and receptor-specific parts of the RNA binding site. Latter are required for specific dsRNA binding by LGP2 RD and could confer pattern selectivity between RIG-I-like receptors. Our data furthermore suggest that LGP2 RD modulates RIG-I-dependent signaling via competition for dsRNA, another pattern sensed by RIG-I, while a fully functional LGP2 is required to augment MDA5-dependent signaling.

PubMed: 19208642
DOI: 10.1093/NAR/GKP059

実験手法

X-RAY DIFFRACTION (2.6 Å)