Calpain-1

Calpain-1

Crystal structure of Calpain-1.

Calpain-1 is a calcium-dependent protease enzyme that plays a crucial role in various cellular processes. It is encoded by the CAPN1 gene and is a member of the calpain protein family. Calpain-1 is primarily found in the cytoplasm of cells and is involved in the regulation of protein degradation and signal transduction pathways.

Structure

The crystal structure of Calpain-1 has been extensively studied, revealing important insights into its function. It consists of two subunits, a large catalytic subunit and a smaller regulatory subunit. The catalytic subunit contains the active site responsible for proteolysis, while the regulatory subunit helps in the activation and regulation of the enzyme. The overall structure of Calpain-1 resembles a pair of scissors, with the catalytic subunit acting as the blades and the regulatory subunit as the handles.

Function

Calpain-1 is involved in a wide range of cellular processes, including cell signaling, cytoskeletal remodeling, and apoptosis. It is known to cleave various target proteins, leading to their activation or inactivation. One of the well-studied targets of Calpain-1 is spectrin, a cytoskeletal protein involved in maintaining cell shape and integrity. Calpain-1-mediated cleavage of spectrin disrupts the cytoskeleton, allowing cellular remodeling and migration.

Role in Disease

Calpain-1's role in disease development.

Dysregulation of Calpain-1 activity has been implicated in several diseases. For example, increased Calpain-1 activity has been observed in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. In these conditions, excessive Calpain-1 activity leads to the degradation of key proteins involved in neuronal function, contributing to the progression of the disease.

Furthermore, Calpain-1 has also been associated with muscle disorders. Mutations in the CAPN1 gene can lead to a loss of Calpain-1 function, resulting in muscular dystrophy. Calpain-1 is involved in the degradation of muscle proteins, and its dysregulation can lead to muscle fiber damage and weakness.

Regulation

The activity of Calpain-1 is tightly regulated to prevent excessive proteolysis and maintain cellular homeostasis. It is primarily activated by an increase in intracellular calcium levels. Calcium binds to the regulatory subunit of Calpain-1, inducing a conformational change that allows the catalytic subunit to cleave target proteins. Additionally, Calpain-1 activity is also regulated by endogenous inhibitors, such as calpastatin, which binds to the catalytic subunit and inhibits its proteolytic activity.

See Also

• Calpain-2
• Protease
• Cytoskeleton