Dipeptidyl-peptidase I

Dipeptidyl-peptidase I

Crystal structure of Dipeptidyl-peptidase I.

Dipeptidyl-peptidase I (DPP I), also known as cathepsin C, is a lysosomal cysteine protease enzyme that plays a crucial role in the immune system. It is encoded by the CTSC gene in humans and is highly conserved across species.

Structure

DPP I is a homodimeric enzyme, with each monomer consisting of multiple domains. The crystal structure of DPP I reveals a globular shape with a central catalytic domain and several auxiliary domains. The catalytic domain contains the active site, where the proteolytic activity of the enzyme takes place. The auxiliary domains are involved in protein-protein interactions and contribute to the stability and function of the enzyme.

Function

DPP I is primarily expressed in immune cells, such as neutrophils, macrophages, and dendritic cells. It plays a crucial role in the activation of various immune cells and the processing of immune-related proteins. DPP I is involved in the maturation of several important immune cell surface receptors, including the T-cell receptor and the B-cell receptor. It also activates several pro-inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α.

Clinical Significance

Mutations in the CTSC gene that encodes DPP I have been associated with Papillon-Lefèvre syndrome (PLS), a rare autosomal recessive disorder characterized by palmoplantar keratoderma and severe periodontitis. In individuals with PLS, the lack of functional DPP I leads to impaired immune cell activation and dysregulation of immune responses.

DPP I has also been implicated in various pathological conditions, including cancer, chronic obstructive pulmonary disease (COPD), and rheumatoid arthritis. In cancer, DPP I has been shown to promote tumor invasion and metastasis by facilitating the degradation of extracellular matrix proteins. In COPD, increased DPP I activity has been observed in the lungs, contributing to the destruction of lung tissue. In rheumatoid arthritis, DPP I is involved in the activation of immune cells and the production of pro-inflammatory cytokines.

See Also

• Cathepsin C
• Protease
• Immune system
• Papillon-Lefèvre syndrome