Structure of an Interleukin-1β Mutant with Reduced Bioactivity Shows Multiple Subtle Changes in Conformation That Affect Protein-Protein Recognition

Abstract

Site-specific mutagenesis was used to obtain the human interleukin-1β mutant protein with glycine substituted for threonine at position 9 (IL-1β Thr9Gly). The mutant maintains receptor binding but exhibits significantly reduced biological activity. The crystal structure of IL-1β Thr9Gly has been determined at 2.4-Å resolution by molecular replacement techniques and refined to a crystallographic R-factor of 19.0%. IL-1β Thr9Gly crystallizes in a different space group (P6522) than does native IL-1β (P43); thus the molecules pack differently. Their overall structure is similar, nevertheless, with both composed of 153 amino acids which form 12 antiparallel β-strands. However, significant conformational differences both close to and far from the site of the mutation may explain the mutant's altered properties. © 1993, American Chemical Society. All rights reserved.