ISG15 is an interferon-induced ubiquitin-like protein that is conjugated to target proteins via the sequential action of three enzymes that are also induced by interferon. Unlike ubiquitin, which is highly conserved, the sequence of ISG15 varies between species. ISG15 conjugation inhibits many viruses, and free (unconjugated) ISG15 can also act as an antiviral protein. Here we focus on the antiviral role of ISG15 conjugation and on countermeasures employed by several viruses. The countermeasure by influenza B virus is unique in that it exhibits species-specificity. Only the antiviral activity of human and non-human primate ISG15s can be blocked, providing one possible explanation for the restriction of influenza B virus to humans.
SUMMARY
Folding and trafficking of low density lipoprotein receptor (LDLR) family members, which play essential roles in development and homeostasis, is mediated by specific chaperones. The Boca/Mesd chaperone family specifically promotes folding and trafficking of the YWTD β-propeller-EGF domain pair found in the ectodomain of all LDLR members. Limited proteolysis, NMR spectroscopy, analytical ultracentrifugation and x-ray crystallography were used to define a conserved core comprised of a structured domain that is preceded by a disordered N-terminal region. High-resolution structures of the ordered domain were determined for homologous proteins from three metazoans. Seven independent protomers reveal a novel ferrodoxin-like superfamily fold with two distinct β-sheet topologies. A conserved hydrophobic surface forms a dimer interface in each crystal, but these differ substantially at the atomic level, indicative of non-specific hydrophobic interactions that may play a role in the chaperone activity of Boca/Mesd family.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.