Interleukin 1 receptor antagonist is a member of the interleukin 1 gene family: Evolution of a cytokine control mechanism

Journal Article · Sat Jun 15 04:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.12.5232· OSTI ID:5934533

Eisenberg, S P; Brewer, M T; Verderber, E; Heimdal, P; Brandhuber, B J; Thompson, R C ^[1]

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1. Synergen, Boulder, CO (United States)

Interleukin 1 receptor antagonist (IL-1ra) is a protein that binds to the IL-1 receptor and blocks the binding of both IL-1{alpha} and-{beta} without inducung a signal of its own. Human IL-1ra has some sequence identity to human IL-1{beta}, but the evolutionary relationship between these proteins has been unclear. The authors show that the genes for human, mouse, and rat IL-1ra are similar to the genes for IL-1{alpha} and IL-1{beta} in intron-exon organization, indicating that gene duplication events were important in the creation of this gene family. Furthermore, an analysis of sequence comparisons and mutation rates for IL-1{alpha}, IL-1{beta}, and IL-1ra suggests that the duplication giving rise to the IL-1ra gene was an early event in the evolution of the gene family. Comparisons between the mature sequences for IL-1ra, IL-1{alpha}, and IL-1{beta} suggest that IL-1ra has a {beta}-stranded structure like to IL-1{alpha} and IL-1{beta}, consistent with the three proteins being related. The N-terminal sequences of IL-1ra appear to be derived from a region of the genome different modes of biosynthesis and suggesting an explanation for their different biological activities.

• OSTI ID: 5934533
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:12; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOLOGICAL EVOLUTION
DNA
DNA SEQUENCING
GENES
GROWTH FACTORS
LYMPHOKINES
MAMMALS
MAN
MEMBRANE PROTEINS
MICE
MITOGENS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RATS
RECEPTORS
RECOMBINANT DNA
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES