PMID- 16979683
OWN - NLM
STAT- MEDLINE
DCOM- 20070319
LR  - 20181113
IS  - 0042-6822 (Print)
IS  - 0042-6822 (Linking)
VI  - 358
IP  - 1
DP  - 2007 Feb 5
TI  - Variola virus IL-18 binding protein interacts with three human IL-18 residues 
      that are part of a binding site for human IL-18 receptor alpha subunit.
PG  - 211-20
AB  - Interleukin-18 (IL-18) plays an important role in host defense against microbial 
      pathogens. Many poxviruses encode homologous IL-18 binding proteins (IL-18BP) 
      that neutralize IL-18 activity. Here, we examined whether IL-18BP neutralizes 
      IL-18 activity by binding to the same region of IL-18 where IL-18 receptor 
      (IL-18R) binds. We introduced alanine substitutions to known receptor binding 
      sites of human IL-18 and found that only the substitution of Leu5 reduced the 
      binding affinity of IL-18 with IL-18BP of variola virus (varvIL-18BP) by more 
      than 4-fold. The substitutions of Lys53 and Ser55, which were not previously 
      known to be part of the receptor binding site but that are spatially adjacent to 
      Leu5, reduced the binding affinity to varvIL-18BP by approximately 100- and 
      7-fold, respectively. These two substitutions also reduced the binding affinity 
      with human IL-18R alpha subunit (hIL-18Ralpha) by 4- and 2-fold, respectively. 
      Altogether, our data show that varvIL-18BP prevents IL-18 from binding to IL-18R 
      by interacting with three residues that are part of the binding site for 
      hIL-18Ralpha.
FAU - Meng, Xiangzhi
AU  - Meng X
AD  - Department of Microbiology and Immunology, The University of Texas Health Science 
      Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
FAU - Leman, Michael
AU  - Leman M
FAU - Xiang, Yan
AU  - Xiang Y
LA  - eng
GR  - K22 AI053230/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060918
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (Interleukin-18)
RN  - 0 (Receptors, Interleukin-18)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Binding Sites
MH  - Interleukin-18/genetics/*metabolism
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Protein Binding
MH  - Protein Interaction Mapping
MH  - Receptors, Interleukin-18/*metabolism
MH  - Surface Plasmon Resonance
MH  - Variola virus/*metabolism
MH  - Viral Proteins/*metabolism
PMC - PMC1800912
MID - NIHMS17407
EDAT- 2006/09/19 09:00
MHDA- 2007/03/21 09:00
PMCR- 2008/01/31
CRDT- 2006/09/19 09:00
PHST- 2006/07/08 00:00 [received]
PHST- 2006/08/07 00:00 [revised]
PHST- 2006/08/12 00:00 [accepted]
PHST- 2006/09/19 09:00 [pubmed]
PHST- 2007/03/21 09:00 [medline]
PHST- 2006/09/19 09:00 [entrez]
PHST- 2008/01/31 00:00 [pmc-release]
AID - S0042-6822(06)00577-0 [pii]
AID - 10.1016/j.virol.2006.08.019 [doi]
PST - ppublish
SO  - Virology. 2007 Feb 5;358(1):211-20. doi: 10.1016/j.virol.2006.08.019. Epub 2006 
      Sep 18.