Characterisation of the human serine protease HTrA1

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The HtrA family represents a new class of oligomeric serine proteases in which a catalytic domain is combined with one or more C-terminal PDZ domains. These proteins are widely conserved and can be found in most organisms. However, the biological implications of only some bacterial HtrAs are known while the human HtrAs are not well characterised and their precise functions are not understood. Our previous work indicated that human HtrA1 is involved in amyloid precursor protein processing, arthritis and cancer linking its function to severe human diseases. It is therefore timely to initiate studies aiming at a precise understanding of biochemical and structural properties, biological functions and its regulation. For this purpose a combination of in vitro biochemistry, crystallography, cell culture and in vivo models will be used. The latter will be instrumental to determine the basic phenotype of gene disruption and, in the future, the potency of specific HtrA1 inhibitors that could be of therapeutic relevance.