Recombinant Human CLPP protein

CLPP (Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit) is a highly conserved ATP-dependent protease belonging to the Clp protease family, primarily localized in the mitochondrial matrix. It plays a critical role in maintaining mitochondrial proteostasis by degrading misfolded, damaged, or surplus proteins. Structurally, CLPP forms a ring-shaped tetradecameric complex, often working in concert with regulatory ATPase subunits like CLPX or CLPA to recognize and process substrates. Its proteolytic activity is essential for mitochondrial protein quality control, stress response, and metabolic regulation, particularly under conditions such as oxidative stress or energy deprivation.

Recombinant CLPP proteins are engineered using heterologous expression systems (e.g., *E. coli* or mammalian cell lines) to study its biochemical functions, substrate specificity, and interactions. These proteins enable researchers to dissect CLPP's role in mitochondrial dynamics, apoptosis, and diseases linked to mitochondrial dysfunction, including neurodegenerative disorders (e.g., Parkinson’s disease), cancer, and metabolic syndromes. For instance, CLPP dysregulation has been implicated in impaired clearance of toxic protein aggregates, contributing to disease progression.

The production of recombinant CLPP involves codon optimization, affinity tag fusion (e.g., His-tag), and chromatographic purification, often followed by activity assays to validate functionality. Its applications span structural studies (cryo-EM, X-ray crystallography), drug screening for CLPP modulators, and gene therapy research. Challenges remain in maintaining the protein’s native conformation and activity *in vitro*, as well as understanding tissue-specific regulatory mechanisms. Ongoing research aims to leverage recombinant CLPP for therapeutic strategies targeting mitochondrial disorders and aging-related pathologies.