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 RIG-like receptors (retinoic acid-inducible gene-I-like receptors, RLRs) are a type of intracellular pattern recognition receptor involved in the recognition of viruses by the innate immune system. RIG-I (retinoic-acid inducible gene or DDX58) is ...

dsRNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

helicase Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that in humans is encoded by the ''DHX58''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. The

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

encoded by the gene DHX58 is known as LGP2 (Laboratory of Genetics and Physiology 2).

Structure and function

LGP2 was first identified and characterized in the context of

mammary tissue A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in prima ...

in 2001, 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 RIG-I (retinoic acid-inducible gene I) is a cytosolic pattern recognition receptor (PRR) responsible for the type-1 interferon (IFN1) response. RIG-I is an essential molecule in the innate immune system for recognizing cells that have been infect ...

and

MDA5 MDA5 (melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the ''IFIH1'' gene in humans. MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and ...

. Since LGP2 lacks

CARD Card or The Card may refer to: * Various types of plastic cards: **By type ***Magnetic stripe card *** Chip card *** Digital card **By function ***Payment card ****Credit card **** Debit card ****EC-card ****Identity card ****European Health Insur ...

domains, its effect on downstream antiviral signaling is likely due to interaction with dsRNA viral

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

or the other RLRs (RIG-I and MDA5). LGP2 has been shown to directly interact 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, 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. Overexpression of LGP2 is able to inhibit RIG-I-mediated antiviral signaling both in the presence and absence of viral ligands. 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. Although LGP2 binds to dsRNA with higher affinity, it is dispensable for RIG-I-mediated recognition of synthetic dsRNA ligands. RIG-I, when overexpressed and in LGP2 knock-down studies, has been shown to induce antiviral response in the absence of viral ligand.

Structure and function

References

Further reading