D
IPR003502

Interleukin-1 propeptide

InterPro entry
Short nameIL-1_propep

Description

The N-terminal of Interleukin-1 is approximately 115 amino acids long, it forms a propeptide that is cleaved off to release the active interleukin-1. This entry represents the propeptide.

Interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis
[1]
. Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors
[2]
. The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors.

Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location
[3]
. The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1RA).

The crystal structures of IL1A and IL1B
[4]
have been solved, showing them to share the same 12-stranded β-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors
[5]
. The β-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel β-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding.

The Vaccinia virus genes B15R and B18R each encode proteins with N-terminal hydrophobic sequences, possible sites for attachment of N-linked carbohydrate and a short C-terminal hydrophobic domain
[6]
. These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons reveal that the gene products are related to each other (20% identity) and to the Ig superfamily. The highest degree of similarity is to the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. A novel method for virus immune evasion has been proposed in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6, preventing these cytokines reaching their natural receptors
[6]
. A similar gene product from Cowpox virus (CPV) has also been shown to specifically bind murine IL-1 beta
[7]
.

References

1.cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, Grubin CE, Wignall JM, Jackson JL, Call SM. Science 241, 585-9, (1988). View articlePMID: 2969618

2.Cloning and characterization of an alternatively processed human type II interleukin-1 receptor mRNA. Liu C, Hart RP, Liu XJ, Clevenger W, Maki RA, De Souza EB. J. Biol. Chem. 271, 20965-72, (1996). View articlePMID: 8702856

3.A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. McMahan CJ, Slack JL, Mosley B, Cosman D, Lupton SD, Brunton LL, Grubin CE, Wignall JM, Jenkins NA, Brannan CI. EMBO J. 10, 2821-32, (1991). View articlePMID: 1833184

4.Crystallographic refinement of interleukin 1 beta at 2.0 A resolution. Priestle JP, Schar HP, Grutter MG. Proc. Natl. Acad. Sci. U.S.A. 86, 9667-71, (1989). View articlePMID: 2602367

5.beta-Trefoil fold. Patterns of structure and sequence in the Kunitz inhibitors interleukins-1 beta and 1 alpha and fibroblast growth factors. Murzin AG, Lesk AM, Chothia C. J. Mol. Biol. 223, 531-43, (1992). View articlePMID: 1738162

6.Two vaccinia virus proteins structurally related to the interleukin-1 receptor and the immunoglobulin superfamily. Smith GL, Chan YS. J. Gen. Virol. 72 ( Pt 3), 511-8, (1991). PMID: 1826022

7.Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Spriggs MK, Hruby DE, Maliszewski CR, Pickup DJ, Sims JE, Buller RM, VanSlyke J. Cell 71, 145-52, (1992). View articlePMID: 1339315

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