DHX58

Description

The DHX58 (DExH-box helicase 58) is a protein-coding gene located on chromosome 17.

DHX58, also known as LGP2, is a protein encoded by the DHX58 gene. It is a RIG-I-like receptor dsRNA helicase enzyme, which plays a role in innate antiviral immunity. LGP2 was first identified in mammary tissue, but its primary function is in the immune response. It is crucial for generating effective antiviral responses against viruses recognized by RIG-I and MDA5. Despite lacking the CARD domains found in RIG-I and MDA5, LGP2 interacts with dsRNA viral ligands and other RLRs, influencing downstream signaling. LGP2 directly interacts with RIG-I through its C-terminal repressor domain (RD), potentially through contact between the RD of LGP2 and the CARD or helicase domain of RIG-I. The helicase activity of LGP2 is essential for its positive regulation of RIG-I signaling. However, LGP2 overexpression can inhibit RIG-I-mediated antiviral signaling, both with and without viral ligands, through a mechanism independent of ligand binding and competition.

DHX58 is a key regulator of antiviral signaling, specifically modulating the activity of RIG-I and MDA5, which are essential for recognizing viral RNA and triggering an immune response. Despite its role in this pathway, DHX58 cannot initiate signaling on its own as it lacks the necessary CARD domain. DHX58 exhibits both positive and negative regulatory functions, and its exact role can be influenced by the specific virus or host cell involved. Inhibition of RIG-I signaling can occur through various mechanisms, including: competing with RIG-I for viral RNA binding, preventing RIG-I dimerization and interaction with MAVS/IPS1, and interfering with IKBKE binding to MAVS/IPS1. On the other hand, DHX58 positively regulates signaling by unwinding viral RNA, making it more accessible for recognition by RIG-I and MDA5. DHX58 is involved in the innate immune response against various RNA and DNA viruses, including poxviruses, SARS-CoV-2, and the bacterial pathogen Listeria monocytogenes. It binds both single-stranded and double-stranded RNA, with a preference for double-stranded RNA and a particular affinity for 5'-triphosphorylated RNA. DHX58 exists as a monomer in the absence of double-stranded RNA but forms a homodimer in its presence. It interacts with RIG-I (through its CARD domain), MAVS/IPS1, and DDX60, and is found in complexes with RIG-I and MDA5. DHX58 also interacts with ANKRD17 and directly binds to ATG5 and ATG12, both as monomers and conjugates.

DHX58 is also known as D11LGP2, D11lgp2e, LGP2, RLR-3.

Associated Diseases

WES Whole Exome Sequencing