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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2006-10-16
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pubmed:abstractText |
The orthopoxviruses ectromelia virus (ECTV) and vaccinia virus (VACV) express secreted gamma interferon binding proteins (IFN-gammaBPs) with homology to the ligand binding domains of the host's IFN-gamma receptor (IFN-gammaR1). Homology between these proteins is limited to the extracellular portions of the IFN-gammaR1 and the first approximately 200 amino acids of the IFN-gammaBPs. The remaining 60 amino acids at the C termini of the IFN-gammaBPs contain a single cysteine residue shown to be important in covalent dimerization of the secreted proteins. The function of the remaining C-terminal domain (CTD) has remained elusive, yet this region is conserved within all orthopoxvirus IFN-gammaBPs. Using a series of C-terminal deletion constructs, we have determined that the CTD is essential for IFN-gamma binding despite having no predicted homology to the IFN-gammaR1. Truncation of the ECTV IFN-gammaBP by more than two amino acid residues results in a complete loss of binding activity for both murine IFN-gamma and human IFN-gamma (hIFN-gamma), as measured by surface plasmon resonance (SPR) and bioassay. Equivalent truncation of the VACV IFN-gammaBP resulted in comparable loss of hIFN-gamma binding activity by SPR. Full-length IFN-gammaBPs were observed to form higher-ordered structures larger than the previously reported dimers. Mutants that were unable to bind IFN-gamma with high affinity in SPR experiments failed to assemble into these higher-ordered structures and migrated as dimers. We conclude that the unique CTD of orthopoxvirus IFN-gammaBPs is important for the assembly of covalent homodimers as well as the assembly of higher-ordered structures essential for IFN-gamma binding.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-10211839,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-10725549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-10954546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-11842249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-12124459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-12543935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-12743266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-14675635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-15105546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-15193916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-15215403,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-1546448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-15546383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-1560532,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-15608205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-15653741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-15749121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-16227218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-16581912,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-2548160,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-3112559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-364941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-7609027,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-8894380,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16928759-9520445
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-538X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10675-82
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16928759-Amino Acid Sequence,
pubmed-meshheading:16928759-Animals,
pubmed-meshheading:16928759-Binding Sites,
pubmed-meshheading:16928759-Carrier Proteins,
pubmed-meshheading:16928759-Cell Line,
pubmed-meshheading:16928759-Cercopithecus aethiops,
pubmed-meshheading:16928759-Dimerization,
pubmed-meshheading:16928759-Ectromelia virus,
pubmed-meshheading:16928759-Humans,
pubmed-meshheading:16928759-Interferon-gamma,
pubmed-meshheading:16928759-Ligands,
pubmed-meshheading:16928759-Molecular Sequence Data,
pubmed-meshheading:16928759-Mutagenesis,
pubmed-meshheading:16928759-Protein Binding,
pubmed-meshheading:16928759-Protein Structure, Quaternary,
pubmed-meshheading:16928759-Protein Structure, Secondary,
pubmed-meshheading:16928759-Protein Structure, Tertiary,
pubmed-meshheading:16928759-Recombinant Proteins,
pubmed-meshheading:16928759-Sequence Deletion,
pubmed-meshheading:16928759-Sequence Homology, Amino Acid,
pubmed-meshheading:16928759-Transfection,
pubmed-meshheading:16928759-Vaccinia virus,
pubmed-meshheading:16928759-Viral Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
The unique C termini of orthopoxvirus gamma interferon binding proteins are essential for ligand binding.
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pubmed:affiliation |
Saint Louis University, Department of Molecular Microbiology and Immunology, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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