Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1993-3-23
|
| pubmed:abstractText |
Monocyte-derived interleukin 1 (IL-1) mediates a wide range of biological effects including destruction of the cartilage matrix in articular diseases such as rheumatoid and osteoarthritis. To elucidate further the relationships between protein structure and biological activities, we have analyzed the sequence of several IL-1 polypeptides using the algorithm of Parker, the hydrophobic cluster analysis method and published structural data. This led us to identify several residues that seemed to be strictly topologically conserved, with respect to identifiable secondary structures features, although this was not readily apparent from sequence alignments. We performed site-directed mutagenesis on some of these conserved residues, as well as on those predicted to occur in external loops of the polypeptide. Human IL-1 beta mutant polypeptides were expressed in Escherichia coli in soluble form and purified to homogeneity by anion-exchange and gel-filtration chromatography. Their biological effects (binding to EL4-6.1 murine thymocytes, Raji human B cells and rabbit chondrocytes cells, lymphocyte activation, neutral protease induction, proteoglycan degradation and synthesis) have been determined. Among the 20 IL-1 beta mutant polypeptides we present here, four showed a markedly reduced activity in cartilage matrix assays without any significant change in their binding to the cartilage matrix cells (chondrocytes). Furthermore, some of these mutants were specific partial agonists of the effects of IL-1 on connective tissue since they have a low affinity for thymocytes.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0014-2956
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
211
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
583-90
|
| pubmed:dateRevised |
2007-7-23
|
| pubmed:meshHeading |
pubmed-meshheading:8436117-Amino Acid Sequence,
pubmed-meshheading:8436117-Animals,
pubmed-meshheading:8436117-B-Lymphocytes,
pubmed-meshheading:8436117-Binding, Competitive,
pubmed-meshheading:8436117-Cartilage,
pubmed-meshheading:8436117-Cattle,
pubmed-meshheading:8436117-Cell Line,
pubmed-meshheading:8436117-Escherichia coli,
pubmed-meshheading:8436117-Humans,
pubmed-meshheading:8436117-Interleukin-1,
pubmed-meshheading:8436117-Mice,
pubmed-meshheading:8436117-Molecular Sequence Data,
pubmed-meshheading:8436117-Molecular Structure,
pubmed-meshheading:8436117-Mutagenesis, Site-Directed,
pubmed-meshheading:8436117-Protein Structure, Secondary,
pubmed-meshheading:8436117-Rabbits,
pubmed-meshheading:8436117-Rats,
pubmed-meshheading:8436117-Receptors, Interleukin-1,
pubmed-meshheading:8436117-Structure-Activity Relationship,
pubmed-meshheading:8436117-T-Lymphocytes
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Interleukin-1 beta-specific partial agonists defined by site-directed mutagenesis studies.
|
| pubmed:affiliation |
Department of Biotechnology, Rhône-Poulenc Rorer, Vitry-sur-Seine, France.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|