title: Structure of interleukin 1 alpha at 2.7-A resolution.
abstract: The interleukin 1 (IL-1) family of proteins has a central role in modulating immune and inflammatory responses. Two major IL-1 proteins, designated alpha (IL-1 alpha) and beta (IL-1 beta), are produced by activated macrophages and other cell types. In an effort to understand the similarities and differences in the physicochemical and functional properties of these two proteins, a program was initiated to determine their structures. Crystals of IL-1 alpha were grown, and the three-dimensional structure at 2.7-A resolution was solved. The technique of multiple-wavelength anomalous dispersion (MAD) with the selenomethionine form of IL-1 alpha was utilized in combination with a single mercury derivative to provide the starting phases. Partial refinement of the IL-1 alpha model has been performed as well. The overall structure is composed of 14 beta-strands and a 3(10) helix. The core of this structure is a capped beta-barrell that possesses 3-fold symmetry and displays a topology similar to that observed for IL-1 beta [Priestle, J. P., et al. (1988) EMBO J. 7, 339-343] and soybean trypsin inhibitor (STI) [McLachlan, A. D. (1979) J. Mol. Biol. 133, 557-563]. In this paper, the overall structure of IL-1 alpha and the nature and fidelity of the internal 3-fold symmetry are discussed. Comparisons with IL-1 beta and STI are made within these contexts.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
authors.forename: B J
authors.initials: BJ
authors.lastname: Graves
authors.forename: M H
authors.initials: MH
authors.lastname: Hatada
authors.forename: W A
authors.initials: WA
authors.lastname: Hendrickson
authors.forename: J K
authors.initials: JK
authors.lastname: Miller
authors.forename: V S
authors.initials: VS
authors.lastname: Madison
authors.forename: Y
authors.initials: Y
authors.lastname: Satow
mesh_terms: D000595:Amino Acid Sequence; D003196:Computer Graphics; D006801:Humans; D007375:Interleukin-1; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D007375:Interleukin-1; D011994:Recombinant Proteins