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Interleukin-1α (IL-1α) is a proinflammatory cytokine and a key player in host immune responses in higher eukaryotes. IL-1α has pleiotropic effects on a wide range of cell types, and it has been extensively studied for its ability to contribute to various autoimmune and inflammation-linked disorders, including rheumatoid arthritis, Alzheimer's disease, systemic sclerosis and cardiovascular disorders. Interestingly, a significant proportion of IL-1α is translocated to the cell nucleus, in which it interacts with histone acetyltransferase complexes. Despite the importance of IL-1α, little is known regarding its binding targets and functions in the nucleus. We took advantage of the histone acetyltransferase (HAT) complexes being evolutionarily conserved from yeast to humans and the yeast SAGA complex serving as an epitome of the eukaryotic HAT complexes. Using gene knock-out technique and co-immunoprecipitation of the IL-1α precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped the IL-1α-binding site to the HAT/Core module of the SAGA complex. We also predicted the 3-D structure of the IL-1α N-terminal domain, and by employing structure similarity searches, we found a similar structure in the C-terminal regulatory region of the catalytic subunit of the AMP-activated/Snf1 protein kinases, which interact with HAT complexes both in mammals and yeast, respectively. This finding is further supported with the ability of the IL-1α precursor to partially rescue growth defects of snf1Δ yeast strains on media containing 3-Amino-1,2,4-triazole (3-AT), a competitive inhibitor of His3. Finally, the careful evaluation of our data together with other published data in the field allows us to hypothesize a new function for the ADA complex in SAGA complex assembly.
Pubmed ID: 22879895
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Network service for comparing protein structures in 3D. You submit the coordinates of a query protein structure and Dali compares them against those in the Protein Data Bank (PDB). You receive an email notification when the search has finished. In favourable cases, comparing 3D structures may reveal biologically interesting similarities that are not detectable by comparing sequences. Requests can also be submitted by e-mail to dali-server at helsinki dot fi. The body of the e-mail message must contain atomic coordinates in PDB format. If you want to know the structural neighbours of a protein already in the Protein Data Bank (PDB), you can find them in the Dali Database. If you want to superimpose two particular structures, you can do it in the pairwise DaliLite server. Academic users may download the DaliLite program for local use.
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