Human interleukin 1: structure-function relationship.
The pleiotropic activities of IL-1 have fostered a series of studies on the structure-function relationship in these proteins. The most extensively studied in this respect has been human IL-1 beta. It has been shown that enzymatic cleavage of the precursor protein to generate the mature polypeptide appears necessary for its full biological activity. The almost complete integrity of the mature IL-1 beta protein is also required for its ability to bind to the receptor and trigger cellular functions. However, by the use of monoclonal antibodies and recombinant or synthetic peptides, it has been possible to map some IL-1 beta regions important for different activities. Both N-terminal and C-terminal fragments are important for receptor binding. A domain around amino acids 187-204 is apparently involved in the hyperalgesic effects of IL-1 beta. Finally, the fragment in position 163-171 appears to be responsible for a restricted series of the IL-1 beta activities, mainly directed to the immune system, although irrelevant for inflammation-related effects and unable of binding to the IL-1R. The understanding of the structure-function relationship of IL-1 obtained so far is expected to give rise within a short time to a new generation of synthetic and/or recombinant derivatives to be experimented for clinical purposes.
Boraschi
D
D
Laboratorio di Immunofarmacologia, Centro di Ricerche Sclavo, Siena, Italy.
Tagliabue
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins