Dataset Information

N-terminal domain of nuclear IL-1? shows structural similarity to the C-terminal domain of Snf1 and binds to the HAT/core module of the SAGA complex.

ABSTRACT: Interleukin-1? (IL-1?) is a proinflammatory cytokine and a key player in host immune responses in higher eukaryotes. IL-1? 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-1? is translocated to the cell nucleus, in which it interacts with histone acetyltransferase complexes. Despite the importance of IL-1?, 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-1? precursor with TAP-tagged subunits of the yeast HAT complexes, we mapped the IL-1?-binding site to the HAT/Core module of the SAGA complex. We also predicted the 3-D structure of the IL-1? 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-1? precursor to partially rescue growth defects of snf1? 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.

SUBMITTER: Zamostna B

PROVIDER: S-EPMC3412866 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

N-terminal domain of nuclear IL-1α shows structural similarity to the C-terminal domain of Snf1 and binds to the HAT/core module of the SAGA complex.

Zamostna Blanka B Novak Josef J Vopalensky Vaclav V Masek Tomas T Burysek Ladislav L Pospisek Martin M

PloS one 20120806 8

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 ...[more]

PMID: 22879895

Similar Datasets

Project description:HIV integrase (HIV-IN), one of three HIV enzymes, is a target for the treatment of AIDS, but the full biological assembly has been difficult to characterize, hampering inhibitor design. The recent crystallographic structures of integrase from prototype foamy virus (PFV-IN) with bound DNA were a breakthrough, revealing how viral DNA organizes two integrase dimers into a tetramer that has the two active sites appropriately spaced for insertion of the viral DNA into host DNA. The organization of domains within each PFV-IN protein chain, however, varies significantly from that found in HIV-IN structures. With the goal of identifying shared structural characteristics, the interactions among components of the PFV-IN and HIV-IN assemblies were investigated with the macromolecular docking program DOT. DOT performs an exhaustive, rigid-body search between two macromolecules. Computational docking reproduced the crystallographic interactions of the PFV-IN catalytic and N-terminal domains with viral DNA and found similar viral DNA interactions for HIV-IN. Computational docking did not reproduce the crystallographic interactions of the PFV-IN C-terminal domain (CTD). Instead, two symmetry-related positions were found for the PFV-IN CTD that indicate formation of a CTD dimer between the two active sites. Our predicted CTD dimer is consistent with cross-linking studies showing interactions of the CTD with viral DNA that appear to be blocked in the PFV-IN structures. The CTD dimer can insert two arginine-rich loops between the two bound vDNA molecules and the host DNA, a region that is unoccupied in the PFV-IN crystallographic structures. The positive potential from these two loops would alleviate the large negative potential created by the close proximity of two viral vDNA ends, helping to bring together the two active sites and assisting host DNA binding. This study demonstrates the ability of computational docking to evaluate complex crystallographic assemblies, identify interactions that are influenced by the crystal environment, and provide plausible alternatives.

Dataset Information

N-terminal domain of nuclear IL-1? shows structural similarity to the C-terminal domain of Snf1 and binds to the HAT/core module of the SAGA complex.

Publications

N-terminal domain of nuclear IL-1α shows structural similarity to the C-terminal domain of Snf1 and binds to the HAT/core module of the SAGA complex.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets