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 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.
Graves
B J
BJ
Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Hatada
M H
MH
Hendrickson
W A
WA
Miller
J K
JK
Madison
V S
VS
Satow
Y
Y
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
D007375:Interleukin-1; D011994:Recombinant Proteins