STRUCTURE OF INTERLEUKIN 1-ALPHA AT 2.7-A RESOLUTION

The interleukin 1 (IL-1) family of proteins has a central role in modulating immune and inflammatory responses. Two major IL-1 proteins, designated α (IL-lα) and ß (IL-1ß), 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-lα were grown, and the three-dimensional structure at 2.7-Å resolution was solved. The technique of multiple-wavelength anomalous dispersion (MAD) with the selenomethionine form of IL-1α was utilized in combination with a single mercury derivative to provide the starting phases. Partial refinement of the IL-lα model has been performed as well. The overall structure is composed of 14β-strands and a 310 helix. The core of this structure is a capped β-barrell that possesses 3-fold symmetry and displays a topology similar to that observed for IL-1β [Priestie, J. P., et al. (1988) EMBOJ. 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-lα and the nature and fidelity of the internal 3-fold symmetry are discussed. Comparisons with IL-β and STI are made within these contexts. © 1990, American Chemical Society. All rights reserved.