Human cathepsin X belongs to the cathepsin family of 11 lysosomal cysteine proteases. We expressed recombinant procathepsin X in Pichia pastoris in vitro and cleaved it into its active mature form using aspartic cathepsin E. We found, using size exclusion chromatography, X-ray crystallography, and small-angle X-ray scattering, that cathepsin X is a biologically active homodimer with a molecular weight of ~53 kDa. The novel finding that cathepsin X is a dimeric protein opens new horizons in the understanding of its function and the underlying pathophysiological mechanisms of various diseases including neurodegenerative disorders in humans.

人组织蛋白酶X属于11个溶酶体半胱氨酸蛋白酶的组织蛋白酶家族。我们在毕赤酵母中体外表达了重组组织蛋白酶X，并使用天冬氨酸组织蛋白酶E将其切割成其活性成熟形式。使用尺寸排阻色谱，X射线晶体学和小角度X射线散射，我们发现组织蛋白酶X是一种具有约53 kDa分子量的生物活性同型二聚体。组织蛋白酶X是一种二聚体蛋白的新发现为了解其功能以及人类包括神经退行性疾病在内的各种疾病的潜在病理生理机制开辟了新的视野。