Cytokine Receptor Domain structure

Fig. 11.2. Domain structure of cytokine receptors. Schematic representation of the domain structure of selected cytokine receptors. WS motif conserved WSXWS sequence (W tryptophan S serine X non-conserved amino add) IL interleukin EpoR receptor for erythropoietin GHR growth hormone receptor LIF-R leukemia inhibitory factor receptor G-CSFR granulocyte colony stimulating factor receptor IFNR interferon receptor TNFR tumor necrosis factor receptor NGFR nerve growth factor receptor Fas, CD40 transmembrane receptors of lymphocytes.

The structures of three cytokine receptor C2HRs and tissue factor (TF) have been determined (see Table I and Chill et al., 2003 Harlos et at, 1994 Josephson et al, 2001 Randal and Kossiakoff, 2001 Thiel et al., 2000 Walter et al, 1995). The general features of the C2HR are shown in Fig. 8. It consists of two /3-sandwich domains, D1 and D2, connected by a short linker containing 1 turn of a- or 3io helix. The cytokine binding site is comprised predominantly of the loops located at the D1 and D2 interface. The N-terminal D1 domain is most distal from the cell membrane, while the G-terminal D2 domain is followed by a short tether of 5-12 amino acids in length before the beginning of the transmembrane helix. 

Muller, Y. A., Kelley, R. F., and de Vos, A. M. (1998). Hinge bending within the cytokine receptor superfamily revealed by the 2.4 A crystal structure of the extracellular domain of rabbit tissue factor. Protein Sci. 7, 1106-1115. 

Fig. 6.6 Cytokine receptors have on their extracellular side a variety of different structural domains. Type I receptors have fibronectin-like domains, type III receptors have cysteine-rich domains, and type IV receptors have immunoglobulin-like regions. Type I receptors have intracellular, membrane-proximal Box 1 and Box 2 regions, which are docking sites for the JAK2 tyrosine kinase with which type I receptors primarily associate. (Reproduced from Fig. lA. p. 252 of ref. 33, with permission of Professor Taniguchi and Science.)...

The effects of cytokines are mediated by specific surface receptors, several of which have now been cloned (Shepherd, 1991). Many of the cloned cytokine receptors have a primary structure which differs from the seven transmembrane spanning segments associated with G-protein-coupled receptors. Thus, the receptor for TNEa is a 55 kD protein which has recently been cloned and appears to have a single transmembrane spanning helical segment, an extracellular domain which binds TNFa and an intracellular domain (Sprang, 1990). The intracellular... 

One common feature of the cytokine receptor family, including the IL-6 family, is that its members contain immunoglobulin (Ig)-like domains, of which the structures are similar to that of Ig, in the extracellular site of each subunit (Bazan 1991). Near the C-terminal end of the second domain ( C-terminal domain), there is a cytokine receptor family consensus sequence, W(Trp)-S(Ser)-X(a variable residue)-W-S. 

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