Cytokines Belong to Four Structural Families

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

Interleukin Structure
(b) Interleukin 4
Primary Structure

FIGURE 12-4

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.]

Hematopoietin Family
Cytokine promotion of activation, differentiation, proliferation, or cell death of T cells, B cells, macrophages, dendritic cells, NK cells, and other leukocytes.

FIGURE 12-5

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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Responses

  • Mika-Matti Wahlman
    Which cytokines belong to which group?
    8 years ago

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