Nature Structural & Molecular Biology11, 1084 - 1091 (2004)
Published online: 17 October 2004; | doi:10.1038/nsmb846
Regulated interactions of mtHsp70 with Tim44 at the translocon in the mitochondrial inner membrane
Patrick D'Silva1, Qinglian Liu1, 2, William Walter1
& Elizabeth A Craig1
1
Department of Biochemistry, 433 Babcock Drive, University of Wisconsin−Madison, Madison, Wisconsin 53706, USA.
2
Present address: Department of Biochemistry and Biophysics, Columbia University, 650 West 168th Street, New York, New York 10032, USA.
Correspondence should be addressed to Elizabeth A Craig ecraig@wisc.edu
Preproteins synthesized on cytosolic ribosomes, but destined for the mitochondrial matrix, pass through the presequence translocase of the inner membrane. Translocation is driven by the import motor, having at its core the essential chaperone mtHsp70 (Ssc1 in yeast). MtHsp70 is tethered to the translocon channel at the matrix side of the inner membrane by the peripheral membrane protein Tim44. A key question in mitochondrial import is how the mtHsp70-Tim44 interaction is regulated. Here we report that Tim44 interacts with both the ATPase and peptide-binding domains of mtHsp70. Disruption of these interactions upon binding of polypeptide substrates requires concerted conformational changes involving both domains of mtHsp70. Our results fit a model in which regulated interactions between Tim44 and mtHsp70, controlled by polypeptide binding, are required for efficient translocation across the mitochondrial inner membrane in vivo.
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