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Loop substitution as a tool to identify active sites of interleukin-1 beta

PALLA, E ; BENSI, G ; ROSSINI, M ; GALLO, E ; CARINCI, V ; BUGNOLI, M ; BERTINI, F ; PARENTE, L ; MELLI, M ; SOLITO, E ; TORNESE BUONAMASSA, D ; FASSINA, G ; RAUGEI, G ; SPANO, F ; GALEOTTI, C ; MORA, M ; DOMENIGHINI, M

The Journal of biological chemistry, 1993-06, Vol.268 (18), p.13486-13492 [Periódico revisado por pares]

Bethesda, MD: American Society for Biochemistry and Molecular Biology

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Título:
Loop substitution as a tool to identify active sites of interleukin-1 beta
Autor: PALLA, E ; BENSI, G ; ROSSINI, M ; GALLO, E ; CARINCI, V ; BUGNOLI, M ; BERTINI, F ; PARENTE, L ; MELLI, M ; SOLITO, E ; TORNESE BUONAMASSA, D ; FASSINA, G ; RAUGEI, G ; SPANO, F ; GALEOTTI, C ; MORA, M ; DOMENIGHINI, M
Assuntos: Amino Acid Sequence ; Analysis of the immune response. Humoral and cellular immunity ; Animals ; Base Sequence ; Binding Sites ; Biological and medical sciences ; Cells, Cultured ; Dinoprostone - metabolism ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; Immunobiology ; Interleukin-1 - chemistry ; Interleukin-1 - metabolism ; Interleukin-6 - genetics ; Lymphokines, interleukins ( function, expression) ; Mice ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Receptors, Interleukin-1 - metabolism ; Regulatory factors and their cellular receptors ; RNA - biosynthesis ; RNA - metabolism ; Tumor Cells, Cultured
É parte de: The Journal of biological chemistry, 1993-06, Vol.268 (18), p.13486-13492
Descrição: By computer analysis of the amino acid sequence of human interleukin-1 beta (IL-1 beta) and of the human type I IL-1 receptor (IL-1RI), we have identified two hydropathically complementary peptides (Fassina, G., Roller, P. P., Olson, A. D., Thorgeirsson, S. S., and Omichinski, J. G. (1989) J. Biol. Chem. 264, 11252-11257) capable of binding to each other. The sequence of the IL-1 beta peptide corresponds to that of residues 88-99 (loop 7 of the crystal structure of mature IL-1 beta) of mature IL-1 beta, one of the exposed and highly charged regions of the molecule. The substitution of this loop with an amino acid sequence of the same length but different hydropathic profile generates a mutant with drastically reduced binding activity to IL-1RI. In contrast, the binding affinity to the type II IL-1R (IL-1RII) is the same as that of wild type IL-1 beta. The results show that 1) loop 7 is part of the binding site of IL-1 beta to IL-1RI, but not to IL-1RII. 2) The structure of the mutant protein is not grossly altered except locally at the position of the substituted loop. 3) The substitution of amino acids by site-directed mutagenesis of the loop 7 region generates mutants with binding affinity constants slightly lower than that of wild type IL-1 beta and not comparable to that of the loop substitution analogue. 4. All mutants analyzed, including the loop substitutions, are biologically active, confirming the structural integrity of the proteins. We propose a binding site in which the cooperation of several low energy bonds extended over a wide area results in a high affinity complex between IL-1 and the type I receptor.
Editor: Bethesda, MD: American Society for Biochemistry and Molecular Biology
Idioma: Inglês

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Loop substitution as a tool to identify active sites of interleukin-1 beta

PALLA, E ; BENSI, G ; ROSSINI, M ; GALLO, E ; CARINCI, V ; BUGNOLI, M ; BERTINI, F ; PARENTE, L ; MELLI, M ; SOLITO, E ; TORNESE BUONAMASSA, D ; FASSINA, G ; RAUGEI, G ; SPANO, F ; GALEOTTI, C ; MORA, M ; DOMENIGHINI, M

Bethesda, MD: American Society for Biochemistry and Molecular Biology

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