Ssc1, a molecular chaperone of the Hsp70 family, drives preprotein import into the mitochondrial matrix by a specific interaction with the translocase component Tim44. Two other mitochondrial Hsp70s, Ssc3 (Ecm10) and Ssq1, show high sequence homology to Ssc1 but fail to replace Ssc1 in vivo, possibly due to their inability to interact with Tim44. We analyzed the structural basis of the Tim44 interaction by the construction of chimeric Hsp70 proteins. The ATPase domains of all three mitochondrial Hsp70s were shown to bind to Tim44, supporting the active motor model for the Hsp70 mechanism during preprotein translocation. The peptide-binding domain of Ssc1 sustained binding of Tim44, while the peptide-binding domains of Ssc3 and Ssq1 exerted a negative effect on the interaction of the ATPase domains with Tim44. A mutation in the peptide-binding domain of Ssc1 resulted in a similar negative effect not only on the ATPase domain of Ssc1, but also of Ssq1 and Ssc3. Hence, the determination of a crucial Hsp70 function via the peptide-binding domain suggests a new regulatory principle for Hsp70 domain cooperation.

• PMID: 12032075
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Strub A, Röttgers K, Voos W

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