CLPB

ClpB, or caseinolytic protease B, is a highly conserved ATP-dependent chaperone in the Hsp100/Clp family found in bacteria and in the organelles of some plants and algae. It functions as a disaggregase that helps recover proteins and protein complexes that have become insoluble or misfolded under stress, such as heat, oxidative damage, or chemical stress. In bacteria, ClpB works in concert with the DnaK (Hsp70) chaperone system to solubilize and refold aggregated substrates, contributing to thermotolerance and general proteostasis.

Structurally, ClpB is a hexameric AAA+ ATPase. Each subunit contains an N-terminal substrate-binding domain, two nucleotide-binding domains (NBD1 and NBD2) that hydrolyze ATP, and a middle M-domain that forms a coiled-coil region regulating activity and mediating interactions with the DnaK system. The N-terminal domain recognizes and binds protein aggregates, while the central channel of the hexamer mechanically unfolds and translocates substrates through the ring in an ATP-driven process, enabling refolding by the partner chaperones.

Regulation and distribution: ClpB expression is typically induced by heat shock and other proteotoxic stresses, often under control of heat-shock sigma factors in bacteria. It is widespread among bacteria and is found in plant organelles such as chloroplasts and mitochondria, where it contributes to organelle proteostasis and stress tolerance. In some organisms, chloroplast ClpB homologs are essential for thermotolerance.

Applications and research: ClpB is studied as a key component of bacterial stress responses and proteostasis networks. Because it is not present in animals, it is of interest as a potential target for antimicrobial strategies aimed at disabling bacterial heat-shock responses.