title: Regulated cycling of mitochondrial Hsp70 at the protein import channel.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Liu
authors.forename: Patrick
authors.initials: P
authors.lastname: D'Silva
authors.forename: William
authors.initials: W
authors.lastname: Walter
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Marszalek
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Craig
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000494:pharmacology; D006868:Hydrolysis; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008954:Models, Biological; D018832:Molecular Chaperones; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C086039:MGE1 protein, S cerevisiae; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C077016:TIM44 protein, S cerevisiae; D000266:Adenylyl Imidodiphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate