Biology:LGP2
 Generic protein structure example |
Probable ATP-dependent RNA helicase DHX58 also known as RIG-I-like receptor 3 (RLR-3) or RIG-I-like receptor LGP2 (RLR) is a RIG-I-like receptor dsRNA helicase enzyme that in humans is encoded by the DHX58 gene.[1][2] The protein encoded by the gene DHX58 is known as LGP2 (Laboratory of Genetics and Physiology 2).[1][3][4]
Structure and function
LGP2 was first identified and characterized in the context of mammary tissue in 2001,[1] but its function has been found to be more relevant to the field of innate antiviral immunity. LGP2 has been found to be essential for producing effective antiviral responses against many viruses that are recognized by RIG-I and MDA5.[5]
Since LGP2 lacks CARD domains, its effect on downstream antiviral signaling is likely due to interaction with dsRNA viral ligand or the other RLRs (RIG-I and MDA5).[6]
LGP2 has been shown to directly interact[6] with RIG-I through its C-terminal repressor domain (RD). The primary contact sites in this interaction is likely between the RD of LGP2 and the CARD or helicase domain of RIG-I as it is seen with RIG-I self-association,[6] but this has not been confirmed. The helicase activity of LGP2 has been found to be essential for its positive regulation of RIG-I signaling.[5] Overexpression of LGP2 is able to inhibit RIG-I-mediated antiviral signaling both in the presence and absence of viral ligands.[6][7][8] This inhibition of RIG-I signaling is not dependent upon the ability of LGP2 to bind viral ligands and is therefore not due to ligand competition.[3][9] Although LGP2 binds to dsRNA with higher affinity,[8] it is dispensable for RIG-I-mediated recognition of synthetic dsRNA ligands.[5] RIG-I, when overexpressed[3] and in LGP2 knock-down studies,[10] has been shown to induce antiviral response in the absence of viral ligand.
References
- ↑ 1.0 1.1 1.2 "The Stat3/5 locus encodes novel endoplasmic reticulum and helicase-like proteins that are preferentially expressed in normal and neoplastic mammary tissue". Genomics 78 (3): 129–34. Dec 2001. doi:10.1006/geno.2001.6661. PMID 11735219.
- ↑ "Entrez Gene: LGP2 likely ortholog of mouse D11lgp2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=79132.
- ↑ 3.0 3.1 3.2 "Paramyxovirus V proteins interact with the RNA Helicase LGP2 to inhibit RIG-I-dependent interferon induction". J. Virol. 86 (7): 3411–21. April 2012. doi:10.1128/JVI.06405-11. PMID 22301134.
- ↑ "Function and regulation of retinoic acid-inducible gene-I". Crit. Rev. Immunol. 30 (6): 489–513. 2010. doi:10.1615/critrevimmunol.v30.i6.10. PMID 21175414.
- ↑ 5.0 5.1 5.2 "LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses". Proc. Natl. Acad. Sci. U.S.A. 107 (4): 1512–7. January 2010. doi:10.1073/pnas.0912986107. PMID 20080593. Bibcode: 2010PNAS..107.1512S.
- ↑ 6.0 6.1 6.2 6.3 "Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2". Proc. Natl. Acad. Sci. U.S.A. 104 (2): 582–7. January 2007. doi:10.1073/pnas.0606699104. PMID 17190814. Bibcode: 2007PNAS..104..582S.
- ↑ "The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I". J. Immunol. 175 (8): 5260–8. October 2005. doi:10.4049/jimmunol.175.8.5260. PMID 16210631.
- ↑ 8.0 8.1 "Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity". J. Immunol. 175 (5): 2851–8. September 2005. doi:10.4049/jimmunol.175.5.2851. PMID 16116171.
- ↑ "Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I". Nat. Struct. Mol. Biol. 17 (7): 781–7. July 2010. doi:10.1038/nsmb.1863. PMID 20581823.
- ↑ "Unique O-Methoxyethyl Ribose-DNA Chimeric Oligonucleotide Induces an Atypical Melanoma Differentiation-Associated Gene 5-Dependent Induction of Type I Interferon Response". J. Pharmacol. Exp. Ther. 342 (1): 150–62. July 2012. doi:10.1124/jpet.112.193789. PMID 22505629.
Further reading
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. 1997. doi:10.1101/gr.6.9.791. PMID 8889548.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2.". J. Virol. 80 (24): 12332–42. 2007. doi:10.1128/JVI.01325-06. PMID 17020950.
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