Cytokines bind to the receptor gp130 and activate a variety of intracellular responses. Chow et al. have determined a 2.4 angstrom-resolution structure of the ligand-binding and activation domains of gp130 bound to Karposi's sarcoma-associated herpesvirus interleukin-6 (IL-6). A tetrameric signaling complex is formed by interactions between viral IL-6 and the activation domain of human gp130. This assembly reveals why the activation domain is required for formation of a competent signaling complex. The tetramer provides a template to model the hexameric signaling complexes formed between gp130 and human cytokines and shows how the viral cytokine achieves molecular mimicry.
D.-c. Chow, X.-l. He, A. L. Snow, S. Rose-John, K. C. Garcia, Structure of an extracellular gp130 cytokine receptor signaling complex. Science 291, 2150-2155 (2001). [Abstract] [Full Text]
