Aran-Guiu X.,Barcelona Institute for Research in Biomedicine |
Ortiz-Lombardia M.,CNRS Architecture and Functions of Biological Macromolecules Lab |
Oliveira E.,Plataforma de Proteomica |
Bonet Costa C.,Barcelona Institute for Research in Biomedicine |
And 3 more authors.
Biochemistry | Year: 2010
GAGA is a Drosophila transcription factor that shows a high degree of post-translational modification. Here, we show that GAGA factor is acetylated in vivo. Lysine residues K325 and K373 on basic regions BR1 and BR3 of the DNA binding domain, respectively, are shown to be acetylated by PCAF. While BR1 is strictly required to stabilize DNA binding, BR3 is dispensable. However, acetylation of both lysine residues, either alone or in combination, weakens the binding to DNA. Despite the high degree of conservation of K325 and K373 in flies, their mutation to glutamine does not affect DNA binding. Molecular dynamics simulations, using acetylated K325 and a K325Q mutant of GAGA DNA binding domain in complex with DNA, are fully consistent with these results and provide a thermodynamic explanation for this observation. We propose that while K325 and K373 are not essential for DNA binding they have been largely conserved for regulatory purposes, thus highlighting a key regulatory system for GAGA factor in flies. © 2010 American Chemical Society.
Muntane G.,Idibell Hospital Universitari Of Bellvitge |
Janue A.,Idibell Hospital Universitari Of Bellvitge |
Fernandez N.,Idibell Hospital Universitari Of Bellvitge |
Odena M.A.,Plataforma de Proteomica |
And 8 more authors.
Neurochemistry International | Year: 2010
Transgenic mice expressing both wild mouse α-synuclein and the Parkinson's disease associated A53T mutated human α-synuclein were subjected to long-term diets impoverished in n-3 or diets impoverished in n-3 and supplemented with docosahexaenoic acid (DHA) for 6 months. Transgenic mice evidenced mild phenotype characterized by increased total α-synuclein expression, truncated α-synuclein forms, and abnormal solubility and aggregation, in the absence of Lewy bodies and neurites, and lack of apparent neuronal loss, astrocytosis and microgliosis. These diets produced a reduction in the content of linolenic, n-3 docosapentaenoic and total polyunsaturated fatty acids, leading to significantly lower double bond and peroxidizability indexes as well as to lower protein oxidative damage, with no effects in α-synuclein expression and with no modifications in the number of cortical astrocytes and microglial cells. The present results show that diets may modify brain lipid composition and susceptibility to oxidative damage that do not interfere with phenotype in models with a genetic susceptibility to develop α-synucleinopathy. © 2009 Elsevier Ltd.