Characterisation of the human serine protease HTrA1

HtrA家族代表了一类新的低聚丝氨酸蛋白酶，其中催化结构域与一个或多个c端PDZ结构域结合。这些蛋白质是广泛保守的，可以在大多数生物体中找到。然而，只有一些细菌的htra的生物学意义是已知的，而人类的htra并没有很好地表征，它们的确切功能也不清楚。我们之前的工作表明，人类HtrA1参与淀粉样蛋白前体蛋白加工、关节炎和癌症，将其功能与严重的人类疾病联系起来。因此，及时开展旨在精确理解其生化和结构特性、生物学功能及其调控的研究。为此目的，将结合体外生物化学、晶体学、细胞培养和体内模型。后者将有助于确定基因破坏的基本表型，并在未来确定可能与治疗相关的特定HtrA1抑制剂的效力。

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.