Human cathepsin X/Z is a biologically active homodimer

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. [Display omitted] •Procathepsin X is activated by cathepsin E into mature form.•Cathepsin X exists as homodimer of Mw of ~53 kDa.•Both cathepsin X molecules exhibit an extensive binding surface.