Helical cytokines

Madej, T., Boguski, M. S., and Bryant, S. H. (1995). Threading analysis suggests that the obese gene product may be a helical cytokine. FEES Lett. 373, 13-18. 

Figure 6. Ribbon diagram of the human IFNy receptor (grey) in a complex with hlFNy (black grey). The two identical receptor chains flank the homodimeric, largely helical, cytokine molecule. The membrane proximal region is at the bottom.

Bazan, J. F. (1990a). Haemopoietic receptors and helical cytokines. Immunol. Today 11, 350-354. 

Walter, M. R. (2002). Crystal structures of alpha-helical cytokine-receptor complexes We ve only scratched the surface. Biotechniques (Suppl. 46 8), 50-57. 

Helical cytokines are secreted proteins that function as intracellular messengers. The information content contained on their a-helical scaffolds is decoded by extracellular high-fidelity interactions with cell surface receptor chains that initiate intracellular signaling cascades leading to diverse cellular functions. Amino acid sequence analysis of the extracellular cytokine binding domains revealed two distinct receptor subclasses, class-1 and class-2 (Bazan, 1990a,b). The a-helical cytokines were subsequently defined based on the class of receptor (class 1 or class 2) they... 

The predominant feature of each o-helical cytokine structure is a left-handed anti-parallel four-helix bundle (Fig. 2) (Presnell and Cohen, 1989 Sprang and Bazan, 1993). The four helices of the bundle are connected by two long overhand connections and one short segment to form a distinct up-up-down-down topology first described for porcine growth hormone... 

Abdel-Meguid et al., 1987). Despite the tremendous explosion in the number of X-ray and NMR structures in the protein data bank in the past 17 years, this simple topology has only been observed for a-helical cytokines. 

Each C2HR is tethered to the membrane by a 5-12 residue linker. This general feature of ct-helical cytokine receptors requires the cytokine binding sites be positioned essentially parallel to the cell membrane. For this to occur in the HCII dimers IFN-7 and IL-10, the two-fold symmetry axis of the molecules must be oriented perpendicular to the cell membrane (Fig. 19). In contrast to the two-fold symmetry axes of IFN-7 and IL-10, GH... 

Chang, C., Magracheva, E., Kozlov, S., Fong, S., Tobin, G., Kotenko, S., Wlodawer, A., and Zdanov, A. (2003). Crystal Structure of Interleukin-19 Defines a New Subfamily of Helical Cytokines. / Biol. Chem. 278, 3308-3313. 

IL-10 is a member of the four a-helical cytokine family and probably functions as a homodimer (160AA)d However, its three-dimensional structure is not yet known. It is a pleiotropic Th2 CD4 lymphocyte cytokine (also Thl in humans) with the capacity to inhibit cell-mediated responses but also to enhance some specific aspects of the immune reaction. This gives it unique immunoregulatory properties. 

Panayotatos, N., Radziejewska, E., Acheson, A., Somogyi, R., Thadani, A., Hendrickson, W.A., McDonald, N.Q., 1995. Localization of functional receptor epitopes on the structure of ciliary neurotrophic factor indicates a conserved, function-related epitope topography among helical cytokines. J. Biol. Chem. 270 (23), 14007-14014. 

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