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

dsRNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself ( non-coding RNA) or by forming a template for the production of proteins ( messenger RNA). RNA and deoxy ...

helicase Helicases are a class of enzymes that are 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 double helix, separating the two hybridized ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

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

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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 that produces milk in humans and other mammals. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in primates (for example, humans ...

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) that can mediate induction of a type-I interferon (IFN1) response. RIG-I is an essential molecule in the innate immune system for recognizing cells that ...

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 f ...

. Since LGP2 lacks

CARD Card or The Card may refer to: Common uses * Plastic cards of various types: **Bank card **Credit card **Debit card **Payment card * Playing card, used in games * Printed circuit board, or card * Greeting card, given on special occasions Arts an ...

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 with a 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 el ...

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