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Molecular Mechanisms for Viral Mimicry of a Human Cytokine: Activation of gp130 by HHV-8 Interleukin-6
- Source :
-
Journal of Molecular Biology . Jan2004, Vol. 335 Issue 2, p641. 14p. - Publication Year :
- 2004
-
Abstract
- Kaposi''s sarcoma-associated herpesvirus (KSHV, or HHV-8) encodes a pathogenic viral homologue of human interleukin-6 (IL-6). In contrast to human IL-6 (hIL-6), viral IL-6 (vIL-6) binds directly to, and activates, the shared human cytokine signaling receptor gp130 without the requirement for pre-complexation to a specific α-receptor. Here, we dissect the biochemical and functional basis of vIL-6 mimicry of hIL-6. We find that, in addition to the “α-receptor-independent” tetrameric vIL-6/gp130 complex, the viral cytokine can engage the human α-receptor (IL-6Rα) to form a hexameric vIL-6/IL-6Rα/gp130 complex with enhanced signaling potency. In contrast to the assembly sequence of the hIL-6 hexamer, the preformed vIL-6/gp130 tetramer can be decorated with IL-6Rα, post facto, in a “vIL-6-dependent” fashion. A detailed comparison of the viral and human cytokine/gp130 interfaces indicates that vIL-6 has evolved a unique molecular strategy to interact with gp130, as revealed by an almost entirely divergent structural makeup of its receptor binding sites. Viral IL-6 appears to utilize an elegant combination of both convergent, and unexpectedly divergent, molecular strategies to oligomerize gp130 and activate similar downstream signaling cascades as its human counterpart. [Copyright &y& Elsevier]
- Subjects :
- *KAPOSI'S sarcoma
*HERPESVIRUS diseases
*INTERLEUKIN-6
*CYTOKINES
Subjects
Details
- Language :
- English
- ISSN :
- 00222836
- Volume :
- 335
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 11610079
- Full Text :
- https://doi.org/10.1016/j.jmb.2003.10.070