ATP-dependent Clp protease proteolytic subunit 1 (ClpP1) (ClpP1)

ATP-dependent Clp protease proteolytic subunit 1 (ClpP1) is a serine protease found in Streptomyces species, notably Streptomyces coelicolor. It serves as a central component of the Clp proteolytic complex, which is responsible for the degradation of misfolded or regulatory proteins within the bacterial cell (UniProt P0A3G7). In Streptomyces, ClpP1 often forms a heterotetradecameric complex with its paralog ClpP2, a configuration essential for normal growth, morphological development, and the regulation of secondary metabolism (PubMed: 23457547). This protease is the molecular target of acyldepsipeptide (ADEP) antibiotics, which were ironically first isolated from Streptomyces hawaiiensis (Nature: 10.1038/nature03348). ADEPs bind to the hydrophobic pockets of ClpP1, inducing a conformational change that widens the axial pore and activates the protease in an ATP-independent manner. This dysregulation leads to the non-specific degradation of essential proteins, causing cell death and making ClpP1 a significant model for antibiotic development against pathogenic bacteria (PubMed: 20651101).

Other names

Caseinolytic protease P1ClpP1 proteaseSerine protease ClpP1ATP-dependent Clp protease proteolytic subunit 1

Allosteric activation and dysregulation of the proteolytic core, leading to ATP-independent, non-specific protein degradation.