SUMMARY PARAGRAPH for MDJ1
Hsp40/DnaJ is a family of proteins, established by bacterial DnaJ, that regulates Hsp70 chaperone activity. Hsp40s stimulate the intrinsically weak ATPase activity of Hsp70 proteins and facilitate Hsp70 interaction with polypeptide substrates. Hsp70 family members often have multiple Hsp40 partners, and these specific pairings govern Hsp70 chaperone involvement in particular processes (reviewed in 5, 6, and 7). All Hsp40s contain a highly conserved 75-amino acid J domain, which interacts with the ATPase domain of Hsp70 to stimulate ATP hydrolysis. However, there are also other conserved structural domains, and based on the presence or absence of these regions, the Hsp40 family can be divided into three subtypes: type I, type II and type III (a comprehensive overview of the structural features of the different HSP40 subtypes can be found in 7). Sequence analysis of the S. cerevisiae genome has revealed 22 proteins in the Hsp40/DnaJ family: YDJ1, XDJ1, APJ1, SIS1, DJP1, ZUO1, SWA2, JJJ1, JJJ2, JJJ3, CAJ1, CWC23, MDJ1, MDJ2, PAM18, JAC1, JID1, SCJ1, HLJ1, JEM1, SEC63, and ERJ5 (7).
Mdj1p is a type I HSP40 protein that acts as a co-chaperone for Ssc1p in the mitochondrial matrix (reviewed in 7 and 8). Mdj1p is not required for assisting Ssc1p during protein import, but instead participates in folding newly imported and nascent peptides, refolding heat-denatured peptides, and preventing aggregation of unfolded proteins as part of an Ssc1p folding complex (Ssc1p-Mge1p-Mdj1p) (9, 2, 4). Mdj1p is also required for degradation of misfolded proteins, proper mitochondrial DNA inheritance, and maintenance of the activity of mitochondrial DNA polymerase Mip1p (3, 10, 11). Loss of Mdj1p activity results in temperature sensitivity, a respiratory defect, and loss of the mitochondrial genome (1, 10). MDJ1 expression is upregulated upon heat shock via binding of the transcription factor Hsf1p to a non-canonical heat shock element present in the MDJ1 promoter (12). Mdj1p can partially substitute for bacterial DnaJ activity, and homologs from plant (GFA2) and human (DNAJA3) are able to complement an mdj1 null strain (13, 14, 15).
Last updated: 2006-12-19