|PROSITE documentation PDOC51789 [for PROSITE entry PS51789]|
Intracellular RIG-I-like receptors (RLRs: retinoic acid-inducible gene I, RIG-I; melanoma differenciation-associated gene 5, MDA-5; and laboratory of genetics and physiology 2, LGP2) recognize viral RNAs as pathogen-associated molecular patterns (PAMPs) and initiate an antiviral immune response. RLRs belong to the superfamily 2 (SF2) helicases or ATPases. Among SF2 ATPases, RIG-I, MDA5, and LGP2 possess a unique domain structure. RIG-I and MDA5 consist of two N-terminal caspase activation and recruitment domains (CARDs) (see <PDOC50209>), a central SF2 type DECH box ATPase domain (consisting of two RecA-like helicase domains, Hel1 and Hel2, and an insert domain, Hel2i) (see <PDOC51192>), and a C-terminal regulatory (CTR) domain. LGP2 lacks the two N-terminal CARDs but contains the DECH box domain, as well as the CTR domain. The CTR domain helps recognize non-self RNAs within the cellular environment. To facilitate the detection of a broad range of non-self RNA targets, each RLR contains a similar but divergent CTR domain that mediates RLR-specific interactions between bound nucleic acids or neighboring patterns [1,2,3,4,5].
The RLR CTR domain is a globular, slightly flattened domain with a concave and a convex side (see <PDB:2W4R>). It is structurally organized in three leaves consisting of two four-stranded (β1, β2, β9, β10 and β5, β6, β7, β8) and one two-stranded (β3, β4) antiparallel β sheets. Small helical turns connect the three β sheets. The two four stranded β sheets are laterally connected by two protruding loops, each containing two highly conserved cysteine residues. Together, the four thiol groups of these cysteines coordinate a zinc ion [4,5].
The profile we developed covers the entire RLR CTR domain.Last update:
February 2016 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Fitzgerald M.E. Rawling D.C. Vela A. Pyle A.M.|
|Title||An evolving arsenal: viral RNA detection by RIG-I-like receptors.|
|Source||Curr. Opin. Microbiol. 20:76-81(2014).|
|2||Authors||Reikine S. Nguyen J.B. Modis Y.|
|Title||Pattern Recognition and Signaling Mechanisms of RIG-I and MDA5.|
|Source||Front. Immunol. 5:342-342(2014).|
|3||Authors||Luo D. Ding S.C. Vela A. Kohlway A. Lindenbach B.D. Pyle A.M.|
|Title||Structural insights into RNA recognition by RIG-I.|
|4||Authors||Cui S. Eisenaecher K. Kirchhofer A. Brzozka K. Lammens A. Lammens K. Fujita T. Conzelmann K.-K. Krug A. Hopfner K.-P.|
|Title||The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I.|
|Source||Mol. Cell 29:169-179(2008).|
|5||Authors||Pippig D.A. Hellmuth J.C. Cui S. Kirchhofer A. Lammens K. Lammens A. Schmidt A. Rothenfusser S. Hopfner K.-P.|
|Title||The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA.|
|Source||Nucleic Acids Res. 37:2014-2025(2009).|