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Point mutations of human interleukin‐1 with decreased receptor binding affinity
Author(s) -
MacDonald H.Robson,
Wingfield Paul,
Schmeissner Ursula,
Shaw Alan,
Clore G.Marius,
Gronenborn Angela M.
Publication year - 1986
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(86)81130-9
Subject(s) - mutant , point mutation , site directed mutagenesis , receptor , mutagenesis , histidine , residue (chemistry) , chemistry , binding site , microbiology and biotechnology , biochemistry , biology , gene , amino acid
Interleukin‐1 (IL‐1) is a monocyte‐derived polypeptide hormone that interacts with a plasma membrane receptor. We have used oligonucleotide‐directed mutagenesis to construct mutant human IL‐1 proteins. Three different point mutants in a unique histidine residue (position 30) exhibited varying degrees of reduced IL‐1 receptor binding affinity, whereas point mutants at five other residues behaved normally. Structural analysis of these mutant proteins by nuclear magnetic resonance spectroscopy detected no (or only minor) conformational changes relative to wild‐type IL‐1. These data suggest that the unique histidine residue influ‐ ences the architecture of the receptor binding site on human IL‐1.