Research
Cell apoptosis involving GRIM-19
The goal of my research is to clarify the functional mechanism of the apoptotic and tumour suppressor protein GRIM-19 and to identify the key residues involved in the binding of GRIM-19 with its partners, using a structural biology approach.
GRIM-19, a gene associated with retinoid interferon-induced mortality 19, has been identified as an interferon (IFN)-beta and retinoic acid (RA) inducible gene that induces cell death. This gene codes for a ≈ 16kDa protein that induces apoptosis in a number of cell lines. The GRIM-19 protein is localized in the mitochondria as a component of NADH:ubiquinone oxidoreductase (complex I) and, it has been shown to be essential for complex I assembly and for its electron transfer activity. It has been demonstrated that some oncogenic proteins bind to the GRIM19 protein and inactivate it, allowing cell proliferation and growth. Namely, GW112 a human anti-apoptotic protein, vIRF1 (viral interferon factor 1) a viral protein encoded by the human Herpes virus 8 (HHV8), E6, an oncoprotein from high-risk human papilloma virus type 16, and U95, a protein from human herpes virus 6. All these proteins bind Grim-19 interfering in this way with the regulation of the cell death response. GRIM-19 also binds the transcription factor STAT3 (signal transducer and activator of transcription 3) and inhibits STAT3-de pendent gene expression. Indeed, Grim 19 as been classified as a tumour suppressor protein. GRIM-19 has also been shown to interact with the nucleotide-binding oligomerization domain 2 (NOD2) and it has been suggested that GRIM-19 may mediate NOD2 function in the recognition of bacterial pathogens.
Dioxygen reduction by the multi-copper oxidases
The multicopper family of enzymes oxidise a variety of substrates, both organic and inorganic, with the concomitant reduction of dioxygen to two molecules of water. They are of significant interest both in the areas of both biotechnology and fundamental structural biology. However the precise details of the reduction/oxidation mechanism are not fully understood. Studies so far have enabled a plausible mechanism to be proposed but several important details require clarification. Our goal is to identify the key determinants of such mechanism using a structural biology approach.
Hydrolysis of Glycosidic Bonds by Cellulases and Hemicellulases
The aim of this research is to understand the enzymatic mechanism carried out by cellulases and hemicellulases and to determine its molecular basis. Moreover, we want to identify the key determinants of these enzymes’ specificity. The ultimate goal of this research is to gather information to engineer these enzymes for biotechnological applications. We are using as model system, the arabinanase (Abn2) and the arabinofunranosidase (Abf2), which have been isolated from the bacteria Bacillus subtilis and are involved in the degradation of arabinan. In addition, we will also use different cellulases and hemicellulases isolated from the fungus Chrysonilia sitophila.
