PROSITE documentation PDOC51789RIG-I-like receptor (RLR) C-terminal regulatory (CTR) domain profile
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.
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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). | |
| PubMed ID | 24912143 | |
| DOI | 10.1016/j.mib.2014.05.004 |
| 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). | |
| PubMed ID | 25101084 | |
| DOI | 10.3389/fimmu.2014.00342 |
| 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. | |
| Source | Cell 147:409-422(2011). | |
| PubMed ID | 22000018 | |
| DOI | 10.1016/j.cell.2011.09.023 |
| 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). | |
| PubMed ID | 18243112 | |
| DOI | 10.1016/j.molcel.2007.10.032 |
| 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). | |
| PubMed ID | 19208642 | |
| DOI | 10.1093/nar/gkp059 |
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