title: Structure of an interleukin-1 beta 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-1 beta mutant protein with glycine substituted for threonine at position 9 (IL-1 beta Thr9Gly). The mutant maintains receptor binding but exhibits significantly reduced biological activity. The crystal structure of IL-1 beta Thr9Gly has been determined at 2.4-A resolution by molecular replacement techniques and refined to a crystallographic R-factor of 19.0%. IL-1 beta Thr9Gly crystallizes in a different space group (P6(5)22) than does native IL-1 beta (P4(3)); thus the molecules pack differently. Their overall structure is similar, nevertheless, with both composed of 153 amino acids which form 12 antiparallel beta-strands. However, significant conformational differences both close to and far from the site of the mutation may explain the mutant's altered properties.
authors.affiliation: Department of Chemistry, Rutgers University, New Brunswick, New Jersey 08903.
authors.forename: N P
authors.initials: NP
authors.lastname: Camacho
authors.forename: D R
authors.initials: DR
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Goldman
authors.forename: B
authors.initials: B
authors.lastname: Schneider
authors.forename: D
authors.initials: D
authors.lastname: Green
authors.forename: P R
authors.initials: PR
authors.lastname: Young
authors.forename: H M
authors.initials: HM
authors.lastname: Berman
mesh_terms: D000595:Amino Acid Sequence; D003196:Computer Graphics; D003460:Crystallization; D005998:Glycine / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D007375:Interleukin-1 / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D012997:Solvents; D013912:Threonine / Q000737:chemistry
chemical_list: D007375:Interleukin-1; D012997:Solvents; D013912:Threonine; D005998:Glycine