PMID- 14672670
OWN - NLM
STAT- MEDLINE
DCOM- 20040203
LR  - 20190710
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 335
IP  - 2
DP  - 2004 Jan 9
TI  - Molecular mechanisms for viral mimicry of a human cytokine: activation of gp130 
      by HHV-8 interleukin-6.
PG  - 641-54
AB  - 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 alpha-receptor. Here, we dissect the biochemical and functional basis of 
      vIL-6 mimicry of hIL-6. We find that, in addition to the 
      "alpha-receptor-independent" tetrameric vIL-6/gp130 complex, the viral cytokine 
      can engage the human alpha-receptor (IL-6Ralpha) to form a hexameric 
      vIL-6/IL-6Ralpha/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-6Ralpha, 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.
FAU - Boulanger, Martin J
AU  - Boulanger MJ
AD  - Department of Microbiology and Immunology, Stanford University School of 
      Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305-5124, USA.
FAU - Chow, Dar-chone
AU  - Chow DC
FAU - Brevnova, Elena
AU  - Brevnova E
FAU - Martick, Monika
AU  - Martick M
FAU - Sandford, Gordon
AU  - Sandford G
FAU - Nicholas, John
AU  - Nicholas J
FAU - Garcia, K Christopher
AU  - Garcia KC
LA  - eng
GR  - R01-AI51321/AI/NIAID NIH HHS/United States
GR  - R01-CA76445/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Antigens, CD)
RN  - 0 (IL6ST protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Viral Proteins)
RN  - 0 (interleukin-6 receptor alpha)
RN  - 133483-10-0 (Cytokine Receptor gp130)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigens, CD/chemistry/*metabolism
MH  - Cytokine Receptor gp130
MH  - Herpesvirus 8, Human/*metabolism
MH  - Humans
MH  - Interleukin-6/chemistry/genetics/*metabolism
MH  - Membrane Glycoproteins/chemistry/*metabolism
MH  - *Molecular Mimicry
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Receptors, Interleukin-6/*physiology
MH  - Sarcoma, Kaposi
MH  - Sequence Homology, Amino Acid
MH  - *Signal Transduction
MH  - Structure-Activity Relationship
MH  - Thermodynamics
MH  - Viral Proteins/chemistry/genetics/*metabolism
EDAT- 2003/12/16 05:00
MHDA- 2004/02/05 05:00
CRDT- 2003/12/16 05:00
PHST- 2003/12/16 05:00 [pubmed]
PHST- 2004/02/05 05:00 [medline]
PHST- 2003/12/16 05:00 [entrez]
AID - S0022283603013780 [pii]
AID - 10.1016/j.jmb.2003.10.070 [doi]
PST - ppublish
SO  - J Mol Biol. 2004 Jan 9;335(2):641-54. doi: 10.1016/j.jmb.2003.10.070.