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Science 4 April 2003:
Vol. 300. no. 5616, pp. 139 - 141
DOI: 10.1126/science.1083379
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Reports

Regulated Cycling of Mitochondrial Hsp70 at the Protein Import Channel

Qinglian Liu,12*dagger Patrick D'Silva,1* William Walter,1 Jaroslaw Marszalek,1ddagger Elizabeth A. Craig1§

Hsp70 of the mitochondrial matrix (mtHsp70) provides a critical driving force for the import of proteins into mitochondria. Tim44, a peripheral inner-membrane protein, tethers it to the import channel. Here, regulated interactions were found to maximize occupancy of the active, adenosine 5'-triphosphate (ATP)-bound mtHsp70 at the channel through its intrinsic high affinity for Tim44, as well as through release of adenosine diphosphate (ADP)-bound mtHsp70 from Tim44 by the cofactor Mge1. A model peptide substrate rapidly released mtHsp70 from Tim44, even in the absence of ATP hydrolysis. In vivo, the analogous interaction of translocating polypeptide would release mtHsp70 from the channel. Consistent with the ratchet model of translocation, subsequent hydrolysis of ATP would trap the polypeptide, driving import by preventing its movement back toward the cytosol.

1 Department of Biochemistry,
2 Graduate Program in Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
*   These authors contributed equally to this work.

dagger    Present address: Department of Biochemistry and Biophysics, Columbia University, 650 West 168th Street, New York, NY 10032, USA.

ddagger    Present address: Department of Molecular and Cellular Biology, Faculty of Biotechnology, University of Gdansk, 80-822, Gdansk, Kladki 24, Poland.

§   To whom correspondence should be addressed. E-mail: ecraig{at}wisc.edu

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