Cytokines structures

Sprang, S.R., Bazan, J.E Cytokine structural taxonomy and mechanisms of receptor engagement. Cun. Opin. 

At the outset of this review, we apologize that we are unable to cite aU contributors to our understanding of this field in our review because of space constraints. We refer the reader to many excellent reviews on various aspects of cytokine structure, receptor interaction, and signaling (Bravo et al, 1998 Davies and Wlodawer, 1995 de Vos et al, 1992 Heinrich et al, 2003 Kossiakoff and De Vos, 1998 Rose-John, 2002 Wells and de Vos, 1996 Wilson andjolliffe, 1999). 

Fig. 3. The gplSO family of cytokines and receptors. Schematic representation of gpl30 and leukemia inhibitory factor receptor (LIFR) oriented in a cell membrane. Of the four-helix bundle gplSO cytokines, structural information currently exists for human interleukin 6 (IL-6) (green) (Somers et al, 1997), human herpes virus interleukin 6 (HlTV-8 IL-6) (purple) (Chow et al, 2001a), ciliary neurotrophic factor (CNTF) (orange) (McDonald et al., 1995), leukemia inhibitory factor (LIF) (blue) (Robinson et al, 1994), and oncostatin-M (OSM) (red) (Deller et al, 2000). Lower panel is a detailed list of gplSO cytokines and the associated receptors incorporated into the final signaling complex. (See Color Insert.)...

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... 

Dumoutier, L., Louahed, J., and Renauld, J. C. (2000a). Cloning and characterization of IL-lO-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to lL-10 and inducible by lL-9./. Immunol. 164, 1814-1819. 

Sprang, S. R., and Bazan, J. F. (1993). Cytokine structural taxonomy and mechanisms of receptor eng ement. Curr. Opin. Struct. Biol. 3, 815-827. 

Like other hormones in this class of cytokines, GH has a four-helix bundle structure as described in Chapter 3 (see Figures 3.7 and 13.18). Two of the a helices, A and D, are long (around 30 residues) and the other two are about 10 residues shorter. Similar to other four-helix bundle structures, the internal core of the bundle is made up almost exclusively of hydrophobic residues. The topology of the bundle is up-up-down-down with two cross-over connections from one end of the bundle to the other, linking helix A with B and helix C with D (see Figure 13.18). Two short additional helices are in the first cross-over connection and a further one in the loop connecting helices C and D. 

Cellular cytokines (interferons, G-CSF) and immune response modifiers originally produced from human cells, most often leukocytes, have now been replaced with recombinant products with well-defined structure/function. Futuristic advances in experimental hematology portend development of human blood cells produced from the hemopoetic stem cells. Yet for the foreseeable future, homologous blood donated by healthy, altruistic voluntary blood donors remains the principal source of safe and adequate supply of blood and blood products for transfusion therapy. 

Bone metabolism comprises the processes of bone formation and bone resorption, the key actions by which skeletal mass, structure and quality are accrued and maintained throughout life. In the mature skeleton, anabolic and catabolic actions are mostly balanced due to the tight regulation of the activity of bone forming ( osteoblast) and bone resorbing ( osteoclast) cells through circulating osteotropic hormones and locally active cytokines. 

Chemokines are a family of small cytokines, or proteins secreted by cells. Proteins are classified as chemokines according to shared structural characteristics such as small size (8-10 kDa in size), and the presence of four... 

Cytokine receptors are a group of structurally related receptors, which couple to the JAK-STAT pathway. Cytokine receptors function as homodimers or heterooligomers. They are divided into two main subclasses, class I, which contains receptors for a variety of hematopoietic growth factors and interleukins and class II, which contains receptors for interferons and interleukins 10, 20/24 and 22. 

Cytokines. Table 1 Structural/funotional groups of cytokines (examples)... 

A vast cascade of cytokines appear to be induced by the presence of this polysaccharide, and immunopoiesis- and hemopoiesis-inhibition are probably the most prevalent during the first two weeks of daily exposure [61]. Studies relating structure to the biological activity have not been performed. 

Chemokines are small chemotactic cytokines that act as important messenger molecules between cells of the immune system. Chemokines produce their effects by activating a family of G-protein-coupled receptors. Chemokine receptors are all seven-transmembrane glycoproteins that are structurally related. They may be characterized into those that bind to specific ligands, or those that bind several chemokine ligands. There are also virally encoded (viral) chemokine receptors that represent shared receptors that have been transduced into the viral genome during evolutionary history (Premack and SchaU 1996). 

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