Point mutations of human interleukin‐1 with decreased receptor binding affinity

Abstract

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.