The crystal structure of C-terminal 10 kDa subdomain of heat shock cognate 70


Chia-Cheng Chou1,2, Chung Wang1and Chwan-Deng Hsiao1

1Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 11529, ROC

2Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC


  70 kDa heat shock protein (Hsp70) chaperones play an essential role in protein folding by preventing the misfolding and aggregation of folding intermidates, under normal and stressed growth conditions. Besides assisting correct folding or guiding the protein translocation across membranes, they can also disassemble oligomeric protein complexes, facilitate unstable proteins into protolytic degradation pathway, and in some cases, regulate the biological activity of specific proteins. The heat shock cognate 70 (Hsc70), belongs to Hsp70 family, is constitutely experessed in the cytosol of the mammalian cells. Structurally, Hsc70 and all Hsp70 family shared the same domain structures. The N-terminal 44 kDa domain is an ATPase, and that the C-terminal 30 kDa domain is thought to be responsible for binding of unfolded proteins or nascent polypeptide substrate. The 30 kDa domain can divided into a N-terminal 18 kDa peptide binding subdomain and a C-terminal 10 kDa subdomains. However, The three dimension structure and function of C-terminal 10kDa subdomain region is still not clear until now. Many evidences suggest that the 10 kDa subdomain participate the self-aggregation without polypeptide substrates binding to regulate the chaperone activity and, the recognition for the accociated proteins to facilitate other specific cellular functions in different Hsp70 family proteins. Here we report the crystal structure of C-terminal 10 kDa subdomain of recombinant rat Rattus norvegicus Hsc70 protein at 3.45Å by multiwavelength anomalous dispersion method. The lemon-shaped crystal belongs to the P6122 space group, and there are four molecules in an asymmetric unit. The four molecules are formed into two antiparallel coiled coil structures, which maybe provide some insights for the stablization in the Hsp70/Hsc70 protein complexes.