6533b83afe1ef96bd12a7c3c
RESEARCH PRODUCT
Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is important for activation of the IL-6 signal transducer, gp130
Hanny Klaasse BosGünther KurapkatFloris D. De HonJoachim GrötzingerStefan Rose JohnLucien A. AardenSaskia B. EbelingJust P. J. Brakenhoffsubject
Models Molecularmedicine.medical_specialtyMolecular Sequence DataBiophysicsBiologyBiochemistryBinding CompetitiveProtein Structure SecondaryMiceStructure-function analysisgp130Structural BiologyMutant proteinAntigens CDLeucineInternal medicineGeneticsmedicineCytokine Receptor gp130Tumor Cells CulturedAnimalsHumansAmino Acid SequenceMolecular BiologyAlanineHybridomasMembrane GlycoproteinsBase SequenceInterleukin-6InterleukinBiological activityCell BiologyReceptors InterleukinGlycoprotein 130Receptors Interleukin-6Protein tertiary structureCell biologyProtein Structure TertiaryEndocrinologyMutationLeucineSignal transductionSequence AlignmentCell DivisionSignal Transductiondescription
A model of the tertiary structure of human IL-6, derived from the crystal-structure of granulocyte-colony stimulating factor, reveals a 5th helical region in the loop between the first and second alpha-helix. To investigate the importance of this region for biological activity of IL-6, residues Glu-52, Ser-53, Ser-54, Lys-55, Glu-56, Leu-58, and Glu-60 were individually replaced by alanine. IL-6.Leu-58Ala displayed a 5-fold reduced biological activity on the IL-6 responsive human cell lines XG-1 and A375. This reduction in bioactivity was shown to be due to a decreased capacity of the mutant protein to trigger IL-6 receptor-alpha-chain-dependent binding to the IL-6 signal transducer, gp130.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1995-08-07 | FEBS Letters |