Shared Signaling Receptors for Hematopoietic Cytokines

IL-ZRp VRC IL-- (common 7c chain) Modeled IL-2 quaternary signaling complex 

The structural basis by which 7(- functions in binding six distinct cytokines is still not defined, although mutagenesis has localized sites of interaction (Olosz and Malek, 2000, 2002). The only member of this family for which a complex structure exists is IL-4 complex, with its alpha receptor (Hage et al, 1999 Mueller et al, 2002). Molecular modeling of the IL-2, IL-4, and IL-7 complexes with 7 have been constructed based on assumed analogies with the GH paradigm of a site I and site II epitope on 

In summary, the 7c class of cytokines clearly utilizes the site I/II architectural assembly of the GH paradigm as the signaling complex, with some important exceptions such as the role of the sushi-domain in the IL-2 and 1L-15Rq . The precise definition of the chemistry of cross-reactive cytokine recognition in this family remains an important future structural challenge. 

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