Homo sapiens (human)
Our immune system protects us from many different harmful agents called pathogens (bacteria, viruses, parasites and fungi). In invertebrates, the immune system is simple involving protective barriers, toxic molecules and phagocytic cells that destroy invading pathogens by ingesting them. In vertebrates, the immune response is of two major forms - innate immune response and the adaptive immune response. The innate immune response is similar to that in invertebrates. It is the response that is first triggered when an infection is recognized and does not depend on whether the host was previously exposed to the infection. The adaptive immune response is a more sophisticated defense mechanism that is triggered by the innate immune response. It is specific to a particular pathogen and depends on the previous exposure of the host to the pathogen. The adaptive immune response is carried out by white blood cells called lymphocytes in two forms - antibody response carried out by lymphocytes called B cells, and cell-mediated response carried out by lymphocytes called T cells. B cells respond by secreting proteins, called antibodies, which bind to the antigen (foreign body or pathogen) to inactivate it and mark it for destruction and ingestion by phagocytic cells. T cells can respond either directly to the signal presented by an antigen by killing the infected cell or by generating a signal to activate the macrophages to destroy the pathogen that they have phagocytosed. Interleukin-18 (IL-18) is a cytokine that is involved in regulating the cell-mediated adaptive immune response in vertebrates. IL-18 binds to its receptor, IL-18R-alpha which heterodimerizes or binds with another receptor, IL18R-beta, to result in the differentiation of naive helper T cells to T helper type I cells along with an increase in Interferon-gamma (IFN-gamma) production and induction of Fas-mediated toxicity. IL-18 is known to function similar to IL-12 but is structurally similar to IL-1-beta (see PDB:1I1B).
The structure here is that of human IL-18 using NMR spectroscopy. The structure consists of three twisted beta-sheets, each with four strands, one short alfa-helix and another 310-helix. The beta-sheets pack together forming a beta-trefoil fold. The structure has three distinct surface patches - I, II and III. Sites I and II, which are located on one side of the beta-trefoil fold and the top of the beta-barrel respectively, are responsible for IL-18 binding to IL-18R-alfa receptor. Site III is located at the bottom of the beta-barrel opposite to site II and is thought to play a role in binding IL18R-beta and hence facilitate the heterodimerization of the two receptors to initiate the signal transduction process.
Protein Data Bank (PDB)
author: Ashwini Patil