Vu MT, Zhai P, Lee J, Guerra C, Liu S, Gustin MC, Silberg JJ

Human mitochondrial DNLZ/HEP regulates the catalytic activity and solubility of the mitochondrial hsp70 chaperone HSPA9. Here, we investigate the role that the DNLZ zinc-binding and C-terminal subdomains play in regulating HSPA9. We show that truncations lacking portions of the zinc-binding subdomain do not affect the solubility of HSPA9 or its ...

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ATPase domain, whereas those containing the zinc-binding subdomain and at least ten residues following this subdomain enhance chaperone solubility. Binding measurements further show that DNLZ requires its zinc-binding subdomain to form a stable complex with the HSPA9 ATPase domain, and ATP hydrolysis measurements reveal that the zinc-binding subdomain is critical for full stimulation of HSPA9 catalytic activity. We also examined if DNLZ is active in vivo. We found that DNLZ partially complements the growth of △zim17 Saccharomyces cerevisiae, and we discovered that a Zim17 truncation lacking a majority of the C-terminal subdomain strongly complements growth like full-length Zim17. These findings provide direct evidence that human DNLZ is a functional ortholog of Zim17. In addition, they implicate the pair of antiparallel β-strands that coordinate zinc in Zim17/DNLZ-type proteins as critical for binding and regulating hsp70 chaperones.

Date: Dec. 07, 2011

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