Caseinolytic peptidase B protein homolog (CLPB)

CLPB (SKD3) is a mitochondrial AAA+ ATPase disaggregase found in the intermembrane space of human mitochondria. It has a distinctive N-terminal ankyrin repeat domain, unlike other canonical AAA+ proteins, which is essential for its higher-order oligomeric assembly and disaggregase activity. The protein uses conserved pore-loops in its ATPase ring to grip and translocate substrate polypeptides, driven by ATP hydrolysis. Its activity regulates mitochondrial proteostasis by solubilizing aggregated mitochondrial proteins; proteolytic activation by PARL protease enhances its function. Mutations in CLPB cause severe metabolic and hematological disorders, such as 3-methylglutaconic aciduria type VII and congenital neutropenia, highlighting its critical roles in human biology and disease etiology[1][2][3][4].

Other names

SKD3Mitochondrial AAA+ disaggregaseHuman ClpBCaseinolytic peptidase B protein homologSkd3

For potential drugs, the expected mechanism would include: - Modulating ATPase activity (activation or inhibition) - Influencing ankyrin domain or rhomboid protease PARL-mediated cleavage (regulation of disaggregase activity) - Enhancing substrate solubilization/disaggregation (therapeutic activation)