Once the genes encoding various cytokines had been cloned, sufficient quantities of purified preparations became available for detailed studies on their structure and function. Cytokines generally have a molecular mass of less than 30 kDa. Structural studies have shown that the cytokines characterized so far belong to one of four groups: the hematopoietin family, the interferon family, the chemokine family, or the tumor necrosis factor family.
The structures of two members of the hematopoietin family, IL-2 and IL-4, are depicted in Figure 12-4. Although the amino acid sequences of these family members differ considerably, all of them have a high degree of a-helical structure and little or no p-sheet structure. The molecules
(a) Interleukin 2
(a) Interleukin 2
Several representations of structures in the hematopoietin family. (a) Left: Topographical representation of the primary structure of IL-2 showing a-helical regions (a and A-D) and connecting chains of the molecule. Right: Proposed three-dimensional model of IL-2. (b) Ribbon model of IL-4 deduced from x-ray crystallographic analysis of the molecule. In (a) and (b) the a helices are shown in red and the p sheets in blue. The structures of other cytokines belonging to the hematopoietin family are thought to be generally similar. [Part (b) from J. L. Boulay and W. E. Paul, 1993, Curr. Biol. 3:573.]
Interaction of antigen with macrophages and the subsequent activation of resting TH cells leads to release of nu merous cytokines (blue arrows), generating a complex network of interacting cells in the immune response.
share a similar polypeptide fold, with four a-helical regions (A-D) in which the first and second helices and the third and fourth helices run roughly parallel to one another and are connected by loops.
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