title: The lid domain of Caenorhabditis elegans Hsc70 influences ATP turnover, cofactor binding and protein folding activity.
abstract: Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy of ATP hydrolysis to alter the folding state of its client proteins. In contrast to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C. elegans (CeHsc70) has not been studied to date.We find that CeHsc70 is characterized by a high ATP turnover rate and limited by post-hydrolysis nucleotide exchange. This rate-limiting step is defined by the helical lid domain at the C-terminus. A certain truncation in this domain (CeHsc70-Δ545) reduces the turnover rate and renders the hydrolysis step rate-limiting. The helical lid domain also affects cofactor affinities as the lidless mutant CeHsc70-Δ512 binds more strongly to DNJ-13, forming large protein complexes in the presence of ATP. Despite preserving the ability to hydrolyze ATP and interact with its cofactors DNJ-13 and BAG-1, the truncation of the helical lid domain leads to the loss of all protein folding activity, highlighting the requirement of this domain for the functionality of the nematode's Hsc70 protein.
authors.affiliation: Center for Integrated Protein Science Munich and Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Franziska T
authors.initials: FT
authors.lastname: Edelmann
authors.forename: Christoph J O
authors.initials: CJ
authors.lastname: Kaiser
authors.forename: Katharina
authors.initials: K
authors.lastname: Papsdorf
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Gaiser
authors.forename: Klaus
authors.initials: K
authors.lastname: Richter
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D009711:Nucleotides / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: C091732:BCL2-associated athanogene 1 protein; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; D046912:Multiprotein Complexes; D009711:Nucleotides; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases