Recombinant Drosophila persimilis Serine protease HTRA2, mitochondrial (HtrA2), is a genetically engineered version of the naturally occurring HtrA2 protein found in Drosophila species. HtrA2 is a mitochondrial serine protease that plays a crucial role in maintaining mitochondrial integrity and function. It is part of the HtrA family of proteases, which are evolutionarily conserved across various species, including humans. The recombinant form of this protein is produced through genetic engineering techniques, allowing for its expression in host organisms like bacteria or yeast for research and therapeutic applications.
HtrA2 is characterized by its unique structure, which includes a mitochondrial targeting sequence, a transmembrane domain, a central protease domain, a PDZ domain, and an IAP-binding motif . The PDZ domain is particularly notable as it recognizes exposed hydrophobic regions of misfolded proteins, facilitating their degradation . HtrA2's role in apoptosis is well-documented; it can promote apoptosis by binding to Inhibitor of Apoptosis Proteins (IAPs) and inhibiting their anti-apoptotic activity .
| Feature | Description |
|---|---|
| Mitochondrial Targeting Sequence | Directs HtrA2 to mitochondria for import and processing. |
| Transmembrane Domain | Anchors HtrA2 within the mitochondrial membrane. |
| Protease Domain | Responsible for the enzymatic activity of HtrA2. |
| PDZ Domain | Recognizes and binds to misfolded proteins for degradation. |
| IAP-Binding Motif | Interacts with IAPs to promote apoptosis. |
HtrA2 is crucial for maintaining mitochondrial function and integrity. Its absence or dysfunction can lead to mitochondrial stress, accumulation of unfolded proteins, and enhanced production of reactive oxygen species (ROS) . These conditions are associated with neurodegenerative diseases, including Parkinson's disease (PD), where HtrA2 has been implicated in pathogenesis . Genetic studies in Drosophila have shown that HtrA2 mutants exhibit phenotypes similar to those of PD models, such as sensitivity to oxidative stress and mitochondrial toxins .
| Condition | Effect of HtrA2 Dysfunction |
|---|---|
| Mitochondrial Stress | Enhanced ROS production and unfolded protein accumulation. |
| Neurodegeneration | Linked to Parkinson's disease through impaired mitochondrial function. |
| Apoptosis | Promotes apoptosis by inhibiting IAPs, contributing to cell death in neurodegenerative contexts. |
Research on recombinant HtrA2 has focused on understanding its role in apoptosis and mitochondrial function. Studies have shown that HtrA2 acts downstream of PINK1 in maintaining mitochondrial integrity but in a pathway parallel to Parkin . The protein's involvement in neurodegenerative diseases makes it a potential target for therapeutic interventions aimed at preserving mitochondrial health.
| Application | Description |
|---|---|
| Therapeutic Targeting | Potential for developing treatments that modulate HtrA2 activity to prevent neurodegeneration. |
| Biological Studies | Used to investigate mitochondrial function and apoptosis mechanisms in various models. |
| Protein Quality Control | Helps understand how misfolded proteins are managed within mitochondria. |
Recombinant Drosophila persimilis Serine protease HTRA2, mitochondrial (HtrA2) is a serine protease exhibiting proteolytic activity against the nonspecific substrate β-casein. It promotes or induces cell death through two mechanisms: (1) direct binding and inhibition of BIRC proteins (inhibitor of apoptosis proteins, IAPs), resulting in increased caspase activity; and (2) a BIRC-independent, caspase-independent mechanism dependent on serine protease activity. It can antagonize the anti-apoptotic activity of IAPs by directly inducing their degradation.
KEGG: dpe:Dper_GL24014