Jdomain

J-domain is a conserved protein module of about 70 amino acids that is found in the DnaJ/Hsp40 family of molecular chaperones. It functions as the activator of the Hsp70 chaperone’s ATPase activity, enabling efficient protein folding, assembly, and maintenance of proteostasis under normal and stress conditions.

The J-domain is typically located at the N-terminus of DnaJ/Hsp40 proteins and contains a highly conserved HPD motif crucial for stimulating Hsp70. Based on additional domains, J-domain proteins are commonly classified into three structural classes. Class I proteins have an N-terminal J-domain followed by a glycine/phenylalanine-rich region, a zinc-binding CRR domain, and a C-terminal substrate-binding domain. Class II proteins lack the zinc-binding region but retain the J-domain and G/F-rich region. Class III proteins consist of a J-domain linked to diverse C-terminal regions and may lack other canonical domains.

Mechanistically, the J-domain interacts with Hsp70 when the latter is in the ATP-bound state, accelerating ATP hydrolysis. This converts Hsp70 to a high-affinity, ADP-bound conformation that binds client proteins. Through this mechanism, J-domain proteins help deliver substrates to Hsp70, regulate client binding and release, and assist in processes such as folding, disaggregation, and targeting misfolded proteins for degradation.

J-domain proteins are evolutionarily conserved across bacteria, archaea, and eukaryotes. Notable examples include Escherichia coli DnaJ, yeast Ydj1, and human DNAJB family members. They play essential roles in stress responses and cellular quality control, and ongoing research continues to elucidate their substrate specificities and regulatory networks.