Coordinated Activation of Hsp70 Chaperones

Hsp70s are a ubiquitous family of molecular chaperones involved in many cellular processes. Two Hsp70s, Lhs1p and Kar2p, are required for protein biogenesis in the yeast endoplasmic reticulum. Here, we found that Lhs1p and Kar2p specifically interacted to couple, and coordinately regulate, their respective activities. Lhs1p stimulated Kar2p by providinga specific nucleotide exchange activity, whereas Kar2p reciprocally activated the Lhs1p adenosine triphosphatase (ATPase). The two ATPase activities are coupled, and their coordinated regulation is essential for normal function in vivo.

[1]  P. Silver,et al.  A yeast DnaJ homologue, Scj1p, can function in the endoplasmic reticulum with BiP/Kar2p via a conserved domain that specifies interactions with Hsp70s , 1995, The Journal of cell biology.

[2]  H. Lin,et al.  The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. , 1993, Molecular biology of the cell.

[3]  M. Egerton,et al.  A novel Hsp70 of the yeast ER lumen is required for the efficient translocation of a number of protein precursors. , 1996, The EMBO journal.

[4]  Ahsen,et al.  Molecular chaperones: towards a characterization of the heat-shock protein 70 family. , 1997, Trends in cell biology.

[5]  J. Tyson,et al.  LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum , 2000, The EMBO journal.

[6]  M. Rose,et al.  Loss of BiP/GRP78 function blocks translocation of secretory proteins in yeast , 1990, The Journal of cell biology.

[7]  R. Schekman,et al.  The Lumenal Domain of Sec63p Stimulates the ATPase Activity of BiP and Mediates BiP Recruitment to the Translocon in Saccharomyces cerevisiae , 1997, The Journal of cell biology.

[8]  L. Hendershot,et al.  Characterization of the Nucleotide Binding Properties and ATPase Activity of Recombinant Hamster BiP Purified from Bacteria (*) , 1995, The Journal of Biological Chemistry.

[9]  Barry P. Young,et al.  Sec63p and Kar2p are required for the translocation of SRP‐dependent precursors into the yeast endoplasmic reticulum in vivo , 2001, The EMBO journal.

[10]  R. Schekman,et al.  A Sec63p-BiP complex from yeast is required for protein translocation in a reconstituted proteoliposome , 1993, The Journal of cell biology.

[11]  Tom A. Rapoport,et al.  Posttranslational protein transport in yeast reconstituted with a purified complex of Sec proteins and Kar2p , 1995, Cell.

[12]  L. Hendershot,et al.  A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. , 2002, Molecular biology of the cell.

[13]  E. Craig,et al.  SSI1 encodes a novel Hsp70 of the Saccharomyces cerevisiae endoplasmic reticulum , 1996, Molecular and cellular biology.

[14]  L. Hendershot,et al.  In Vitro Dissociation of BiP-Peptide Complexes Requires a Conformational Change in BiP after ATP Binding but Does Not Require ATP Hydrolysis (*) , 1995, The Journal of Biological Chemistry.

[15]  T. Rapoport,et al.  Interaction of BiP with the J-domain of the Sec63p Component of the Endoplasmic Reticulum Protein Translocation Complex* , 1999, The Journal of Biological Chemistry.

[16]  M. Makarow,et al.  The Hsp70 Homologue Lhs1p Is Involved in a Novel Function of the Yeast Endoplasmic Reticulum, Refolding and Stabilization of Heat-denatured Protein Aggregates , 1997, The Journal of cell biology.

[17]  Bernd Bukau,et al.  The Hsp70 and Hsp60 Chaperone Machines , 1998, Cell.

[18]  E. Hartmann,et al.  Interaction of Kar2p and Sls1p Is Required for Efficient Co-translational Translocation of Secreted Proteins in the YeastYarrowia lipolytica * , 1998, The Journal of Biological Chemistry.

[19]  J. Beckerich,et al.  Sls1p Stimulates Sec63p-Mediated Activation of Kar2p in a Conformation-Dependent Manner in the Yeast Endoplasmic Reticulum , 2000, Molecular and Cellular Biology.

[20]  J. Tyson,et al.  A novel subfamily of Hsp70s in the endoplasmic reticulum. , 1997, Trends in cell biology.